Method and Device for the in Vitro Analysis for MRNA of Genes Involved in Haematological Neoplasias

Abstract

Method and device for the in vitro analysis of mRNA of genes involved in hematological neoplasias. The device, composed of probes which specifically hybridize with genes involved in hematological neoplasias, designed so that its behaviour in the hybridization is similar, permits the evaluation of the mRNA level in biological samples taken from subjects suspected to be suffering from hematological neoplasia and facilitating the comparison between the different samples and their grouping by similarity in the gene expression patterns, especially when the probes are disposed in the form of microarray. The application of the method of the invention to obtain and process data of gene expression differences from the device of the invention permits the identification of genes significant for distinguishing samples associated to hematological neoplasias, facilitates the diagnosis of neoplasias as CLL and permits making a prognosis of the evolution thereof.

Description

FIELD OF THE INVENTION

[0001] The invention relates to the technical-industrial sector of the extracorporeal in vitro diagnosis of biological samples, by genetic engineering techniques, applied to the diagnosis of specific types of neoplasias from their gene expression patterns and/or to the prognosis of their evolution. More specifically, the invention relates to the identification of neoplasias originating from hematopoietic cells from the evaluation of the levels of messenger RNA of significant genes in biological samples such as peripheral blood samples, preferably by the use of microarrays. With this it is possible to identify samples corresponding to patients suffering from CLL, permitting the diagnosis thereof and, furthermore, it is possible to classify samples from patients suffering from CLL in samples which belong to patients wherein the CLL is going to remain stable or wherein it is going to progress, enabling the prognosis of the future evolution of these patients.

BACKGROUND OF THE INVENTION

[0002] Each day, the human body produces billions of new white and red cells and platelets which replace the hematopoietic cells which are lost as a consequence of a normal process of renewal, disease or trauma. The organized production process of hematopoietic cells and homeostasis is known with the name of hematopoiesis (Weissman I L et al., 2000; Leung A Y H et al., 2005.

[0003] In man, hematopoiesis is confined to the bone marrow (B.M.) of the greater part of the bones, and gradually, with age, this is replaced by fat, which in the adult, 70% of the bone marrow is located in the pelvis, vertebra and sternum (Bernard et al., 1976).

[0004] All the mature blood cells are generated from a relatively low number of hematopoietic cells known hematopoietic stem cells. The hematopoietic stem cell has two characteristics which are the pluripotentiality or capacity to give rise to different hematopoietic cell strains and the self-renewal or property of self-perpetuation, generating cells the same as its self (Weissman I L et al., 2000). This capacity is essential for the maintenance of hematopoiesis throughout the life which, without self-renewal, would quickly exhaust the reserve of available stem cells. Hematopoietic stem cells are capable of generating different mature hematopoietic cell types through a series of intermediate progenitors and precursors. These progenitors and precursors suffer an ordered sequence of events which transform them into mature cells. This process is known with the name of differentiation (Lee M F et al., 2005). The differentiation of the hematopoietic cells involves changes which affect, among others, the size and form of the cell, gene expression, proteins, response to signals and localization of the cells.

[0005] The terminally differentiated cells have lost their capacity for division and suffer apoptosis after a period of time which goes from hours for neutrophils to decades for some lymphocytes. This fact means the B.M. should constantly ensure cell exchange (Datta S R et al., 1999).

[0006] The hematopoiesis process comprises a complex interaction between intrinsic genetic events of the hematopoietic cells and environment wherein they are found. This interaction is that which determines if the hematopoietic precursors and progenitors must stay quiescent, proliferate, be differentiated in one or another line or enter into apoptosis (Domen J et al., 1999). All the genetic and environmental mechanisms which govern the production of blood cells operate by altering the relative balance of these fundamental cell processes.

[0007] Environmental and genetic factors are critical in hematopoiesis. Thus, for example, the gene expression belongings to the Rb families (Bergh et al., 1999), cyclins (Della Ragione F et al., 1997) or Hox (Magli M C et al., 1997) regulate the proliferation of hematopoietic cells at early stages of differentiation. The genes of the bcl-2 family regulate apoptosis in hematopoietic cells (O'Gorman D M et al., 2001). A great variety of genes among which are found C/EBP (Tenen D G et al., 1997), Pax5 (Nutt S L et al., 1999) and lkaros (Nichogiannopoulou A. et al., 1998) seem to be involved in hematopoietic differentiation and line compromise.

Hematological Neoplasias

[0008] Hematological neoplasias are malignant processes which affect any one of the cell types involved in the hematopoietic system. As a consequence of this transformation, the cell is blocked in a stage of differentiation and starts to accumulate due to uncontrolled proliferation, to a failure of the apoptotic mechanisms or a blocking of its differentiation process.

[0009] The malignant transformation of the hematopoietic cells during the different stages they pass through in their differentiation to mature cells originates a great number of different neoplasias (Guttmacher A E et al., 2003). This type of neoplasias is therefore a very heterogeneous group of diseases which only has the hematopoietic origin of the cell type transformed in common.

Classification of Hematological Neoplasias

[0010] Generically, it is possible to establish two groups: lymphoid neoplasias which affect the different cell type and degrees of maturity which form the lymphoid line, both B and T, and the other large group is constituted by the myeloid neoplasis which affect various cell types of the myeloid line. However, this simplistic classification is currently more developed, as detailed below.

[0011] From a clinical standpoint, classically, lymphoma leukemias have been differentiated in arbitrary form, indicating the leukemias as those neoplasias which affect the bone marrow and have peripheral expression, i.e. circulation of anomalous cells in blood, and lymphomas as those neoplasias which remain localized in the lymph nodes or other lymphoid tissues and which lack, at least initially, leukemic behaviour. In the case of leukemias, the acute processes of the chronics has initially been differentiated by the morpho-cytological characteristics of the proliferating cells (immature and atypical in the first case and differentiated in the second) and to the clinical manifestations of the disease. At present, the knowledge of the immunological markers and the genetic alterations which affect the hematopoietic cells help to differentiate the different processes more accurately.

[0012] Today, it is known that hematological neoplasias, as occurs in other types of cancer, have a multigenic origin. The great technological revolution produced in recent years has made it possible to know the molecular basis of several neoplasias. The use of these techniques makes it possible to identify relevant genes in human cancer, confirm the results obtained in basic research in animal models, establish patters of susceptibility, more accurately classify the neoplasias, improve the diagnosis of the disease, identify new therapeutic targets and improve the therapeutic selection for each patient.

[0013] Also, the diversity which exists between individuals is important and has its clinical repercussion, based on the genetic differences: if we are capable of recognising these genetic differences, we will also be capable of advancing in discovering toxicity and differences in response to treatment. (Westbrook C A et al., 2005).

[0014] In 1995, the World Health Organization (WHO) in collaboration with the European Hematology Association and pathologists, clinicians and scientists throughout the world, started a project in order to obtain an agreed classification of the hematopoietic tissue and lymphoid organs. This project led to the development of a system for the definition, classification and establishment of agreed diagnostic criteria for myeloid, lymphoid and histiocytic neoplasias (Jaffe E S et al., 2001). The classification criteria of the WHO are the same used in the REAL (Revised European American Lymphoma) classification published by the International Lymphoma Study Group in 1994 (Harris N L et al., 1994). The REAL classification system, unlike other previous classification systems is based on the definition of "real" entities and not morphological subtypes. All available information is used to establish these "real" entities, i.e. morphological, immunophenotypical and biological data are combined with the genetic and clinical characteristics (Harris N L et al., 1999a).

[0015] The WHO classification, which was presented in 1997, stratifies the entities in accordance with the cell line affected: myeloid, lymphoid, histiocytic/dentritic and mastocytic. Within each category, the disease is defined in accordance with the morphology, immunophenotype, genetic and clinical data (Harris N L et al., 1999b). In many neoplasias, the stage wherein the accumulated tumour cell is found does not coincide with the stage in which the initial transformer event has occurred. Thus, many hematological neoplasias originate in the initial precursors and the specific genetic alteration may determine which cell continues advancing in its differentiating until stopping and accumulating in more advanced stages of differentiation (Shaffer A L et al., 2002). In contrast, other neoplasias can develop in the more advanced stages of differentiation, as occurs in the cells from the follicular centres wherein the genetic translocations and rearranging produce activation of genes which contribute to tumour development. The classification for each entity reflects the best stimulation for its cell line and stage of differentiation, recognising that the knowledge available at present is imperfect and that changes may occur in the assignment to a cell line and in classification as the available knowledge improves.

[0016] The current criteria of diagnosis and classification of these neoplasias are based on a combination of (Braziel R M et al, 2003): [0017] Morphological evaluation of the cell: Observation under the microscope of the cells involved. Information is obtained on the type of cell and degree of its maturity. [0018] Study of the immunophenotype: Recognition of antigens expressed on the surface of the neoplastic cell. These antigens are expressed differently and to different degrees in accordance with the line and of the stage the cell is at. The expression of surface antigens characteristic of the line and stage of differentiation of the cell is known, for example, the expression of CD19 and CD20 is typical of line B cells, whilst the expression of CD3 is typical of line T. The study of CD23 is key when differentiating NHLCM from CLL (Gong J Z et al., 2001).

[0019] An attempt has always been made to relate the different types of neoplasias with their corresponding normal cell population through their morphological and immunophenotypical characteristics. Many neoplasias therefore seem "trapped" in determined stages of development as they have morphological and immunophenotypical characteristics similar to those of the hematopoietic cell at that stage of differentiation (Shaffer A L, et al., 2002). [0020] Clinical characteristics: Signs and symptoms of the patient at the time of diagnosis. [0021] Determination of molecular markers: Measurement of some molecules which are associated to concrete entities such as the presence of PMURARA in promyelocytic leukemia or which give a better or worse prognosis, such as, for example, the expression of CD38 in CLL cells marker of bad prognosis (Durig J et al., 2002) [0022] Cytogenetic studies based on the search for genetic alterations in the DNA of tumour cells. In many cases, specific rearranging occur which are characteristic of types of tumour or stages (Mitelman F, et al., 1997). In accordance with the chromosome translocations, it is possible to establish different groups with clinical significance, for example, in LLA-B, where the presence of fusion oncoproteins is frequent, the presence of t(2;21)/TEL1-AML1 and t(1;19)/E2A-PBX1 is associated with a response to the treatment whilst the prognosis for patients with t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 is much worse (Arico M et al., 2000). Searches are also usually made for specific mutations, deletions or insertions in a gene which have been related to more favourable prognosis such as, for example, the myelodysplastic syndromes associated to 5q- (Boultwood J et al., 1994).

[0023] As has previously been commented, the WHO establishes four large groups of hematological neoplasias in accordance with the strain involved (myeloid, lymphoid, histiocytic/dentritic and mastocytic lines). Below the neoplasias belonging to the myeloid line and the lymphoid line are described in more detail as they are those which arise with greatest frequency. Those corresponding to the histiocytic/dentritic and mastocytic lines for the moment are very isolated entities.

1. Myeloid Neoplasias

[0024] They group together all the neoplasias originated in the myeloid line of differentiation, the WHO distinguishes four large groups (Vardiman J W et al., 2002).

[0025] 1.1 Myeloproliferative Syndromes (MPS)

[0026] Myeloproliferative syndromes (MPS) are clonal alterations of the hematopoietic stem cell characterized by effective hematopoiesis which leads to an increase in the blood levels of one or more hematopoietic and hepatosplenomegaly lines. They constitute a group of entities wherein there exists an increase in precursors of the myeloid series or fibrosis of the bone marrow (myelofibrosis); this group also includes systemic mastocytosis. The following can be highlighted: [0027] Chronic myeloproliferative syndromes (CMPS). Clonal alteration of the hematopoeietic stem cell. Characterized by an effective hematopoiesis which produces increase in peripheral blood of one or more cell lines and frequently hepatosplenomegaly, medullary hypercellularity with maturity but without dysplasia. [0028] Chronic myeloid leukemia (CML). It is a clonal process secondary to an acquired genetic alteration of the pluripotent cell. The disease is characterized by the superproduction of neu trophils and of their precursors. It has three phases: the first called chronic phase of undefined duration, followed by the acceleration phase and finally the blastic crisis which is really secondary acute leukemia.

[0029] CML has a low incidence of approximately one case per 100,000 inhabitants/year and appears most frequently in the sixth and seventh decades of life. It can be considered a rare disease.

[0030] It is the characteristic leukemia par excellence as the term leukaemia was applied to this entity for the first time. 95% of the cases have a genetic marker, the Philadelphia chromosome, originated by the translocation of a fragment of chromosome 22 which adheres to chromosome 9 or t(9;22) (q34;q11). This translocation causes the fusion gene bcr-abl. The protein coded by this chimeric gene, BCR-ABL, has an increased thyrosine-kinase activity compared with the normal abl protein activity as oncogenic growth factor (Pane F et al., 2002), although really the mechanisms which produce the superproduction of myeloid cells are not totally clarified. It is possible that other proto-oncogenes such as p-53 intervene in the process and in the transformation of chronic phase to blastic crisis. The few cases in which the Philadelphia chromosome is detected represent atypical myeloproliferative symptoms and correspond to the variant of MDS known as chronic myelomonocytic leukemia (CMML).

[0031] The diagnosis is based on the high cell counts for the blank series, appearance of morphologically normal myeloid cells and in all the stages of differentiation, but with a high number of myelocytes and neutrophils, there are generally basophilia and thrombocytosis. In the acceleration phase an increase in immature cells occurs in the peripheral blood and in the blastic crisis the predominant cell is the myeloblast (65%) or the lymphoblast (35%). [0032] Vaquez's disease (VD). It is the myeloproliferative syndrome characterized by the increase in mass of the red series. Vazquez's disease is a benign haematological disease, whose suffering does not influence shortening of survival. However, it is a clonal disease which may evolve in 15% of patients to myelofibrosis or acute leukemia (5%). [0033] Essential Thrombocythemia (ET). Myeloproliferative syndrome characterized by platelet production 15 times greater than normal. It may be associated to thrombotic or hemorrhagic complications secondary to platelet dysfunction. It appears at around 60 years of age, with equal incidence in both sexes. [0034] Myelofibrosis (MF). It is a neoplastic clonal disorder of the pluripotent stem cell. It is characterized by a great production of abnormal megakaryocytes. These cells release molecules (growth factor derived from platelets, platelet factor 4) which stimulate the proliferation of fibroblasts and build collagen fibres in the bone marrow. The bone marrow is incapable of functioning normally and the hematopoietic precursor cells translate to the liver and spleen, giving rise to extramedullary hematopoiesis. Characterized by fibrosis of B.M and splenomegaly. It appears in people over 50 years of age and has no preference of sex.

[0035] Mastocytosis. Group of entities characterized by the proliferation of mastocytic cells in different parts of the body. Systemic mastocytosis (SM), is a rare disease which typically affects adults and has bone alterations in 70% of patients (Chen C C et al., 1994).

[0036] 1.2. Myelodysplastic/Myeloproliferative Syndromes (MDS/MPS)

[0037] The WHO has established a somewhat different classification, separating MDS/MPS as entities differentiated from the other MDS, since they share characteristics with the CMPS that make them different. This group includes three entities: chronic myelomonocytic leukaemia, chronic atypical myeloid, leukeumia, juvenile myelomonocytic leukaemia and non-classifiable MDS/MPS. Myelodysplastic syndromes (MDS) are clonal proliferations of the hematopoeietic stem cell which share at the time of diagnosis, clinical, morphological and analytical data which are superimposed between AML and CMPS. They are characterized by the hypercellularity of bone marrow due to the proliferation of one or more myeloid lines (Heaney M L, 1999). The presence of dysplasia in at least one line (myeloid, erythroid or megakaryocytic-platelet) is a characteristic of MDS. The incidence is variable depending on the variety. An incidence of 3 cases.times.100,000 inhabitants over 60/year is estimated. The FAB classification establishes 4 diagnostic categories (Bennett J M et al., 1984): simple refractory anemia (RA), refractory anemia with ring sideroblasts (ARS), refractory anemia excess blasts (RAEB) and refractory anemia with excess blasts in transformation (RAEB-T) and chronic myelomonocytic leukemia (CMML).

[0038] With regard to the MDS, the WHO establishes five differentiated categories (Harris N L, et al., 1999): refractory anemia, refractory cytopenia with multiline dysplasia, refractory anemia with excess blasts, non-classifiable MDS and MDS associated to an isolated defect in chromosome 5 (of the 5q) or syndrome 5q-.

[0039] 1.3. Acute Myeloblastic Leukemia (AML)

[0040] Clonal proliferation of immature cells of the myeloid line. They may appear de novo or secondary in patients with myelodysplastic syndrome (MDS). The classification prepared by the French-American-British group (FAB) considers eight varieties (M0-M7) based on morphological criteria and on the immunophenotype of the neoplastic cells (Bennett J M, et al., 1976). Despite the fact that this classification has been accepted for many years, the discovery that many genetic alterations have a predictive characteristic and the incorporation of the cytogenetic analysis to the diagnosis of acute leukemias (Bene M C et al., 2001) has made it possible to subclassify the disease and establish the evaluation of the prognosis, as occurs with translocation t(15;17) which characterized promyelocytic variety leukemia which is characterized by the expression of a retinoic acid receptor (RAR), characteristic which makes this type of leukaemia sensitive to treatment with transretinoic acid (TRA) in most cases.

[0041] The WHO classifies AML by incorporating morphological, immunophenotypical, genetic and clinical data to be able to define biological homogeneous entities and with clinical relevance. Thus, AML is classified into four large categories: 1.--AML with recurrent genetic anomalies. 2.--AML with multiline dysplasia. 3.--AML related to treatment and 4.--non-classifiable AML (ref WHO). The three first categories recognise the importance of biological factors which predict the evolution of the process. The cytogenic analysis represents the most powerful prognosis factor (Roumier C, et al., 2003). It is used to identify subgroups of AML with different prognosis: low risk with favourable response to treatment (t(8;21), t(15;17) or inv(16)), intermediate risk (normal karyotype or t(9;11) or high risk (inv(3), -5del(5q) or -7del(7q), or more than three alterations). There is molecular heterogeneity within the risk group. In some cases of patients with normal karyotype, the presence of mutations has been found in gene FLT3 (Kottaridis P D, et al., 2001.) and MLL (Dohner K et al., 2002).

[0042] The medullary image in the microscopic examination of aspirate is generally that of invasion by cells similar to one another, of immature morphological characteristics which distort the normal cell distribution constituting authentic cell sheets. Medullary hyperproduction conditions which areas of inactive bone marrow come to again present a new focus of hematopoiesis in the adult age, in this case of abnormal cells.

[0043] Approximately 80-90% of young patients with AML, achieve complete remission of the disease after chemotherapy. However, the majority relapses, and a cure occurs in 30%. The oncogenic transplant of bone marrow has managed to increase the cure rate to 50%, but it is limited by the availability of identical donor HLA. It is therefore a group of neoplasias with diverse genetic abnormalities and variable response to treatment (Giles F J et al., 2002)

2. Lymphoid Neoplasias

[0044] The WHO's classification is a refinement of the REAL classification (Harris N L et al. 1994). Three large groups of lymphoid neoplasias: 1.--Lymphoid neoplasias derived from B cells. 2.--Lymphoid neoplasias derived from T and NK cells. 3.--Hodgkin's lymphoma. This classification includes solid neoplasias and lymphoid leukemias, as in many of them their occurs a transformation from one phase to another and the distinction between them, may be artificial. Thus, chronic lymphatic leukemia B and the lymphocytic NHL are originated by the same cell and represent different manifestations of the same neoplasia, the same occurs with lymphoblastic lymphoma and lymphoblastic leukemia

[0045] 2.1. Neoplasias Derived from B, T and NK Cells

[0046] The WHO's classification divides these neoplasias in accordance with the stage of maturity of the cells in neoplasias of precursor cells and neoplasias of mature cells (WHO Classification Tumours of Haematopoietic and lymphoid tissues. In Pathology and genetics of tumours of Haematopoietic and lymphoid tissues. E S Jaffe, N L Harris, H Stein, J W Vardiman. IARC Press. Lyon, 2001). Due to the high number of entities described, the following are highlighted: [0047] Acute lymphoblastic leukemia (ALL): Clonal proliferation of lymphoid precursors. In approximately 80% of the cases, the precursors belong to the lymphoid B line. The molecular analysis of the genetic alterations of the leukemic cells have significantly contributed to the understanding of the pathogenesis and prognosis of ALL (Ferrando A A et al., 2005). Despite the fact that the frequency of genetic subtypes differs in children and in adults, the general mechanisms which lead to ALL are a consequence of the abnormal expression of proto-oncogenes due to chromosome translocations which create fusion genes or a hyperploidy. This initial oncogenic event is probably insufficient to produce leukemia and it is believed that other alterations which cooperate with this first one are necessary to definitively alter the proliferation and survival of the transformed cell. All these alterations contribute to the leukemic transformation of the hematopoietic stem cells or of their progenitors as they affect key regulating processes, maintaining or increasing their capacity for self-renewal, escape from the normal proliferation controls, blocking of differentiation and promoting resistance to apoptotic signals (Hanahan D, et al., 2000).

[0048] The overall appearance of the bone marrow is similar to that described for myeloid leukemia. The research of the minimal residual disease is important, a factor which condiciona with su presence the probable relapse of the disease. The FAB classification defines 3 stages in accordance with the morphology (L1-L3).

[0049] It is the most frequent leukemia in the childhood, and in the clinical course and the response to treatment depends on the type of genetic alteration, for example, patients with hyperdiploidy have a favourable prognosis when it is treated with treatment schemes which include antimetabolites but, in general terms, children are cured with standard chemotherapy and prophylaxis of the CNS and in adults only 20% have prolonged survival with chemotherapy, the allogenic autologous transplant is useful for cases considered high risk. [0050] Chronic lymphatic leukemia (CLL). CLL is characterized by clonal proliferation and accumulation of lymphocytes with mature appearance and resistant to apoptosis in B.M, blood and lymphoid organs (Galton D A, 1966). When the lymphodenopathy is dominant, the clinical symptoms are called Lymphocytic lymphoma. The lymphocytes affected are line B in 95% of the cases and 5% of the cases involve T lymphocytes.

[0051] It is the most frequent leukemia in the Western world. The average age of patients diagnosed is 65 years old, only 10-15% of the cases arise under 50 years (Jemal A et al., 2003). It is the most common cause of leukaemia in adults of the counties of the Western world and involves around 25% of all leukemias. The incidence is 3 cases per each 100,000 inhabitants and year, with a predominance in males, with a male/female proportion of 1.7:1. In recent years, it has increasingly been diagnosed in younger patients. The proportion of cases diagnosed at early stages of the disease (Rai K R, et al., 1975) has increased from 10 to 50%, probably due to an early diagnosis thanks to routine lymphocyte counts. The disease affects more men than women.

[0052] The prognosis and clinical course of the disease is extremely variable. Some patients have a rapidly progressive evolution and die in the 2-3 years after the diagnosis, whilst in others, the course is indolent and they live for 10-20 years without problems related to the CLL. Intermediate cases occur in half of patients.

[0053] Approximately, 20% of patients are asymptomatic at the time of diagnosis, performing this as a consequence of a routine blood analysis. When symptoms exist, they are not specific and include fatigue, weakness and discomfort.

[0054] The Binet classification (Binet J L et al., 1981) defines 3 stages of disease in accordance with the concentration of haemoglobin, number of platelets, number of lymph nodes involved and the presence of visceromegalies. The Rai classification (Rai K R et al., 1975) uses the same indicators but classifies patients in five groups.

[0055] This neoplasia is not characterized by a unique and recurrent genomic alteration. There are some markers which give a more unfavourable prognosis such as the presence of deletions in chromosomes 17 and 11 and those patients with absence of mutations in IgVh genes (40% of the cases) and high proportion of cells expressing CD38 is characterized by a more agressive clinical course and a worse response to treatment (Hamblin T J et al., 1999; Durig J et al., 2002). Another recently described marker is ZAP-70, independent prognosis marker whose expression is indirectly related to the mutational state of the gene of the heavy chains of immunoglobulins (Crespo M et al., 2003). [0056] Multiple myeloma: MM). MM is a malignant disease wherein a clone of plasma cells (terminal cells of the B lymphoid line) of the bone marrow suffers uncontrolled proliferation. It involves 10-15% of all the malignant diseases and is characteristic of advanced ages, only 2% of the cases are diagnosed before 40 years of age. For unknown reasons, the incidence of the disease is increasing.

[0057] These cells produce and secrete monoclonal immunoglobulin or fragments of immunoglobulins, composed by a heavy and light chain class (kappa or lambda). Occasionally, the myeloma cannot be secreted or the protein is not detectable in serum or urine. The neoplastic plasma cell produces other molecules such as IL6, tumour necrosis factor or osteoclast activator factor which contributes to producing osteolysis, hypercalcemia and renal insufficiency, characteristics alterations of the disease.

[0058] The diagnosis can be casual on performing an analysis in patients without symptomology or limited disease (20% of cases). The disease in these patients can remain stable for years and early treatment in the asymptomatic phase does not provide any advantages.

[0059] Patients with monoclonal component but which do not meet the MM diagnosis are considered carriers of monoclonal gammapathy of indeterminate meaning (MGIM). Among 10 and 20% of these patients develop MM in 10 years (Kyle R A, 1997; Zhan F et al., 2002). The monoclonal component can also be associated to other diseases such as lymphoma, non-hematological neoplasias and diseases of the connective tissue. [0060] Lymphoplasmocytoid lymphoma and Waldenstrom's macroglobulinemia. It is the clinical expression of a low-degree lymphoproliterative disease, characterized by the infiltration of anomalous lymphoplasmocytic cells in bone marrow, lymph node and spleen, accompanied by monoclonal production of immunoglobin M, which conditions an increase in blood viscosity and the appearance of haemorrhagic vascular manifestations and by difficulty in circulation in the small vessels. [0061] --Non-Hodgkin's lymphoma (NHL). NHL are solid tumours of the lymphoid tissue which are much more heterogeneous than Hodgkin's disease. The complexity and diversity of the NHL as regards morphology, genetics, phenotype and clinical behaviour has given rise to the existence of multiple classifications, none of them completely satisfactory.

[0062] It is the most frequent hematological disease and, in terms of years of life lost, it is the fourth most important neoplasia of the Western world and it seems that its incidence is increasing.

[0063] It may appear at all ages, but the average appearance is 50 years of age. The cause of the disease is not clear. Specific chromosome translocations have been described associated to certain types of lymphomas, for which reason they are of great use in diagnosis (Montoto S et al., 2003). Most of the Burkitt-type lymphomas present translocation t(8;14), wherein the c-MYC oncogene of chromosome 8 is transferred to the next region in chromosome 14 where the heavy immunoglobins chains are coded. 90% of ollicular lymphomas are characterized by translocation t(14;18), where the bcl-2 gene of the chromosome 18 is transferred to the region of the heavy immunoglobulin chains. It is well known that the overexpression of bcl-2 inhibits apoptosis (programmed cell death). It is easy that this chromosome rearranging requires other stimulation, such as, for example, the coexpression of a second proto-oncogene or an antigenic stimulation to develop the malignant proliferation. An example of combination of multiple combined causes constitute the lymphoma associated to AIDS. The appearance of aggressive extranodal lymphomas is the result of the combination of immunosuppression by HIV, deregulation of a proto-oncogene (c-MYC) and a secondary viral infection (Epstein-Barr's virus), the same occurs in patients subjected to organ transplant (Harris N L et al., 2001).

[0064] The clinical presentation of the disease is more irregular than in Hodgkin's disease. It may behave indolently without requiring immediate treatment or, in contrast, behave aggressively which is quickly fatal.

[0065] The most frequent nodal condition is cervical. As regards extranodal condition, the signs and symptoms depend on the affected organ. The bone marrow appears infiltrated with greater frequency in the low degree NHL and may cause pancytopenia. The presence of malignant cells in peripheral blood is also frequent in low-degree NHL, but of very bad prognosis in those of high-degree.

[0066] The diagnosis is carried out by the histological study of the lymphatic tissue. The additional information is obtained by monoclonal antibodies directed against specific lymphocytic antigens (immunophenotype); this helps to identify the degree of maturity of the malignant cell and determine the T or B origin thereof. The presence of mutation in genes which code Ig in the NHL of strain B are usually used for the identification of some subtypes of NHL (Kuppers R et al., 1999).

[0067] 2.2. Hodgkin's Lymphoma (LH)

[0068] It is an infrequent disease and has predilection for the masculine sex in a proportion of 2/1. It is characterized by the presence of large cells, bi or multi-nucleus called Reed-Sternberg (RS) and other smaller and mononuclear cells which appear in a small quantity in the tumour; the rest of the cells are lymphocytes, granulocytes, fibroblasts and plasma cells. This inflammatory infiltrate probably reflects the immune response of the host with the malignant cells. The nature of the RS and Hodgkin's cells have been greatly studied but continues being disputed. They may be derived from an initial stage of the lymphoid cells.

[0069] In some cases, the existence of DNA for Epstein-Barr's virus has been detected in the tumour. One hypothesis is that the bimodal distribution of the disease is due to the infection in young subjects and the other peak would be caused by average environmental causes.

[0070] The diagnosis is obtained by biopsy of a lymph node. To plan the treatment, it is necessary to determine the extension of the disease. (Kuppers R, 2002; Cossman J, 2001; Devilard E et al., 2002).

Problems in Classification

[0071] The great quantity of hematopoietic cells and the many stages of differentiation through which they pass further complicates the classification of the neoplasis originating from this type of cells. Despite the efforts to establish a classification based on "real" entities, some of the categories are ambiguous and in many cases contain very heterogeneous groups as regards a response to therapy of clinical course. This heterogeneity is that responsible for, on the one hand, the incessant search for markers capable of differentiating some behaviours from others and, on the other hand, that the disputed classification of this type of neoplasis is subjected to continuous revisions.

[0072] An ideal classification system should be precise, reproducible, easy to use and should especially have biological and clinical significance (Chan W C, et al., 2005). The current diagnosis systems and the classification of the hematological neoplasias are based on the recognition of histological and morphological, immunophenotypical and cytogenetic characteristics and study of a molecular marker with prognostic value. However, in some of the diagnostic categories defined in this way, the following is observed: [0073] A marked heterogeneous therapy response. Within the same disease there are patients who reach full remission, partial remission, do not respond, which relapse after a certain therapy. The capacity to predict a response is especially important in this type of neoplasis since the transplant of stem cells is an effective but toxic alternative response. The capacity to determine what patients would respond to a conventional therapy before giving it may be beneficial to be able to apply the most effective treatment to each patient. [0074] A variable clinical behaviour. Within this category there are patients whose disease is going to remain stable for long periods of time and which are not going to need therapy and those whose disease is going to progress rapidly requiring aggressive therapy.

[0075] These variations point to the existence of molecular heterogeneity within the diagnostic categories, differences which the conventional methods of diagnosis are not capable of determining and hence, the search for new forms of analysis which provide a greater resolution in the characterization of this type of neoplasias.

[0076] In this line, the use of expression arrays have demonstrated being effective not only in deciphering the biological and clinical diversity which is found in many tumours, but in understanding the biological and pathological processes which affect many symptoms and, in particular, the hematopoietic system. The expression arrays are ordered arrays of sequences associated to a solid support, complementary to mRNA or to its corresponding cDNA or cRNA, which allow the analysis of the differential expression of hundreds or thousands of genes simultaneously. One of the supports to which they are frequently bound is to rectangular fragments of glass similar to slides, a format which is frequently alluded to by the terms microarray, biochip or, simply, chip. Their use is becoming increasingly frequent for the diagnosis of various diseases or for the evolution of the evaluation of the susceptibility of suffering from them.

First Works of Arrays and Hematological Neoplasias

[0077] In 1999, the Golub group published one of the first articles referring to the role of arrays in the classification of hematological neoplasias (Golub T R et al., 1999). An array with 6817 genes represented was used for the study of expression profiles in AML and ALL. A group of 50 genes was selected with the capacity of predicting the type of leukemia (class predictor) and they were used to classify a group of unknown samples in the correct categories. The study of the expression of these 50 genes is sufficient for the classification of a sample of acute leukemia in AML or ALL. Despite the fact that the distinction between AML and ALL is well established with the current diagnostic methods, the study revealed the existence of specific expression patterns associated with each type of acute leukemia and proved the use of expression profiles in cancer classification.

[0078] In 2000, the Alizadeh group published an article in which a specialized array is used, the lymphochip which contains genes expressed preferentially in lymphoid cells or if which an immunological or oncological importance is known with 17,856 sequences (Alizadeh A A et al., 1999). This group used the "lymphochip" for the study of gene expression patterns associated to differences in clinical behaviour in a Diffuse Large B-Cell Lymphoma (DLCL) (Alizadeh A A, et al. 2000). The DLCL is a NHL with a very heterogeneous behaviour and impossible to distinguish using conventional diagnostic methods: 40% of patients respond well to therapy and have prolonged survival whilst 60% die due to the disease. The authors found that the gene expression could be related to the clinical behaviour of the tumours. This was one of the first articles to speak of arrays for the "subclassification" of hematological neoplasias, i.e. the use of expression profiles for the identification of two different groups of DLCL from the transcriptional standpoint, DLCL subtypes with clinical behaviour impossible to predict with conventional diagnostic criteria.

[0079] At present there are multiple publications wherein, directly or indirectly appear the arrays applied not only to classification and subclassification, but also to the study, diagnosis, prognosis, identification of new markers in haematological diseases (Greiner TC, 2004; Alizadeh A A et al, 2000; Bea S et al., 2005; Dave S S et al., 2004), as well as patent applications which disclose the use of this type of device for the differentiation between different types of hematological neoplasias. Thus, for example, patent application WO2003/008552 discloses the use with diagnostic purposes of differences in the expression pattern of genes to differentiate between mixed line leukemia (MLL), acute lymphoblastic leukemia (ALL) and acute leukemia myelogenous leukemia (AML), defending the possibility of making this differential diagnosis with the data obtained after the diagnosis of samples from patients afflicted by each one of these types of leukemia by the use of commercial chips from Affymetrix. Although genes are indicated with variations in the expression between the three types of leukemias which would permit the differentiation between them, no specific sequences are mentioned other than those present in the Affymetrix chip which could have been used to detect these genes by devices different from those of said company, nor does it consider the design of devices or methods which would permit the diagnosis of other types of leukemias or, in general, neoplasias derived from hematopoietic cells.

[0080] Patent application WO2005/024043, for its part, also relates to the field of gene expression analysis to go into greater detail in the knowledge of differences existing at a molecular level between the different neoplasias derived from hematopoietic cells, specifically centering on the case of lymphomas, to extract data which help in its diagnosis or in the prognosis of its evolution. In particular, it discloses a method to obtain useful functions to predict the evolution of individuals affected by different types of lymphomas evaluating in lymph node biopsies to what extent patterns or genetic prints contribute in each one of them, groups of genes which are expressed in a coordinated manner and which are related to the cell origin of the neoplasia, the different types of non-malignant cells present in the biopsy and the oncogenic mechanisms responsible for cancer. The different patterns or genetic prints are also deduced in this case from the data obtained with commercial chips from Affymetrix. Furthermore, application WO2005/024043 states it provides an alternative microarray, composed of a fewer number of sequences than the Affymetrix microarrays, which would also permit the analysis of differences in gene expression between lymphomas and their application for deducing functions of prediction of survival and for the differentiation between different types of lymphomas. Although it indicates the genes whose analysis would be made possible by that microarray, the specification of application WO2005/024043 does not indicate the sequence of the probes which would compose the microarray, only mentioning that they would be cDNA type and leaving doubts over whether that cDNA would appear complete or the analysis of the corresponding gene expression would be carried out using as probe only one fragment of said cDNA, which would remain tp be determined.

[0081] It would be interesting to have compositions and methods which would permit ifferentiation between neoplasias of hematopoietic origin based on their molecular level difference, specifically designed for this group of neoplasias, wherein it would evaluate the expression of a more reduced number of genes than in the commercial microarrays used in the studies described in the aforementioned patient applications and which enabled both the diagnosis of certain neoplasias and the prediction of their future evolution, thus helping in the prescription of a suitable treatment for each patient, a particularly interesting characteristic in those neoplasias, as is the case of CLL, wherein the prognosis of the future evolution of the patient is difficult with the knowledge and tests available to date. Furthermore, it would be particularly convenient that the probes used to evaluate the expression of the expressed genes had been designed specifically so that, in addition to being specific and with a perfectly defined sequence, all had a similar behaviour, which would make them suitable, in general, to use in combination in a same test and, in particular, to form part of the same ordered array associated to a solid support, such as chips or microarrays. The compositions and methods of this invention meet this need.

[0082] Instead of commercial microarrays to detect genes significant for distinguishing between neoplasias or creating functions which predict the survival of the individual suffering from it, the invention provides new oligonucleotides, of perfectly defined sequence, capable of specifically detecting genes which have been selected as they are known to be significant for the biology of blood cells or for the pathology of different neoplasias, oligonucleotides which also have the feature of having being designed so that they share common characteristics which have a similar behaviour to those used as probes in hybridization, which makes them suitable to be used in compositions which comprise combinations thereof. Said compositions and in particular those wherein these nucleotides are arranged in ordered form on an easy to handle solid support such as glass similar to slides, are suitable for carrying out tests to detect statistically significant genes or differentiate samples taken from individuals suffering from certain types of neoplasias originating from hematopoietic cells of samples taken from individuals not suffering from said neoplasias, as they are compositions which contain a number of nucleotides less than those commercial microarrays designed with a more general purpose, being specifically designed for the analysis of samples from individuals suffering from neoplasias and composed of a known sequence of probes, perfectly reproducible, which are designed to be used together in the same test as they are of similar behaviour. The additional inclusion in the microarrays of the invention of oligonucleotides of low homology with human genes, but chosen so that the rest of their characteristics are similar to those of the oligonucleotides of the invention designed to act as probes capable of recognizing human genes with high specificity, permits the use of said microarrays for the identification of statistically significant genes in the identification of samples associated to certain neoplasias of hematopoietic origin by the use of tests wherein it is feasible to establish controls in all their phases. As shown in the examples which appear further on, in the present specification the use of these microarrays in combination with various statistical techniques permits the correct classification of different biological samples by a method which is precise, reproducible, easy to use and with biological and clinical significance, as they are based on differences of gene expression with significance for the biological processes which are being analysed. In particular, the use of a microarray of the invention in combination with the method of the invention permits the identification of blood samples in patients suffering from chronic lymphatic leukemia (alteration not considered in applications WO2003/008552 and WO2005/024043 and whose diagnosis has not been described by the use of commercial microarrays), distinguishing those of both samples obtained from healthy individuals and samples related to other types of leukemias, and those corresponding to Jurkat or U937 cells, facilitating the diagnosis of CLL through the analysis of expression levels of statistically significant genes to do this and even permitting the obtainment of functions which enable the mathematical calculation of the probability of a sample belonging to individuals afflicted with stable chronic lymphatic leukemia from samples belonging to individuals afflicted with progressive chronic lymphatic leukemia, a distinction which is now difficult to carry out a priori by the available techniques, which means it is a useful and novel tool for the prognosis of the future evolution of individuals afflicted with this disease, individuals whose diagnosis may also have been carried out by compositions and method of the invention or may have been known thanks to the application of a different method, but for which, on having a tool which makes it possible to make a prognosis on how the CLL they are suffering from is going to later evolve, it would be easier to decide if it is suitable to subject them to an immediate aggressive treatment or simply keep them under observation to check that their gene expression data continue indicating that the disease is going to remain stable for a long period of time.

SUMMARY OF THE INVENTION

[0083] The invention provides compositions which include at least one oligonucleotide from the group composed of:

SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, or combinations thereof.

[0084] Said oligonucleotides have been designed so that, in addition to being specific for the corresponding genes whose expression one wants to evaluate, they have a similar behaviour, as they are of similar lengths and all of them have GC in the range of 40% to 60%, in addition to corresponding to zones situated less than 3000 nucleotides from end 3' (poly(A)) of the mRNA which one wants to detect and evaluated and of being constituted by sequences which coincide in their sense with those of the corresponding mRNA. Therefore, they are suitable to be used in the same test or form part of a composition which comprises combinations thereof. A particular embodiment of the invention is constituted by the compositions which comprise mixtures of several of said oligonucleotides. Especially preferred are those compositions which comprise mixtures of oligonucleotides which correspond to genes significant for classifying a sample as associated to a certain neoplasia and/or to determine the future evolution thereof. Especially preferred embodiments of the invention are also those compositions which comprise the totality of the oligonucleotides from the group composed of:

SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG470, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563.

[0085] Additionally, the invention provides oligonucleotides useful to be used as controls in the method of the invention. On the one hand as integrity controls, the pairs of oligonucleotides SG463 and SG464 (complementary, respectively at ends 5' and 3' of the .beta.-actin gene) and SG466 and SG467 (complementary, respectively, to ends 5' and 3' of the GAPD gene) are provided. Additionally, oligonucleotides SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6 and SSPC7 are provided, which may be used as exogenous internal positive controls of the process quality after adding to the sample which contains the starting mRNA molecules of polyadenylated nucleic acids which contain fragments which correspond in their sequence to those of these oligonucleotides (such as the transcripts corresponding to the genes wherefrom said nucleotides are derived) and which are subjected to the same processing as the starting mRNA, as well as oligonucleotides SCN2, SCN3, SCN6, SCN8, SCN11, SCN12 and SCN13, designed to be used as positive hybridization controls and oligonucleotides SCN1, SCN5, SCN7, SCN10, SC1, SC2, SC3, SC4, SC5, SC6 and SC7, designed to be used as negative controls; they all comply with the conditions of having low homology with human genes, in addition to complying with the same conditions of the oligonucleotides complementary to human genes of being of similar lengths and all of them having GC contents in the range of 40% to 60%, correspond to zones situated at less than 3000 nucleotides from end 3' (poly(A)) of the non-human mRNA which would be capable of detecting and being constituted by sequences which coincide in their sense with those of the corresponding mRNA. Any composition which contains at least one of oligonucleotides SG463, SG464, SG466, SG467, SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6, SSPC7, SCN2, SCN3, SCN6, SCN8, SCN11, SCN12, SCN13, SCN1, SCN5, SCN7, SCN10, SC1, SC2, SC3, SC4, SC5, SC6 and SC7, in combination with at least one of the oligonucleotides complementary to human genes of the invention mentioned above is also a composition included in the scope of the present invention.

[0086] It is especially preferred that the oligonucleotides which form part of a composition of the invention are bound to a solid support. In particular, those are preferred of said compositions wherein the distribution of the oligonucleotides on the solid support are of ordered form, whereby the solid support is a rectangular piece of glass similar to a microscope slide and that the oligonucleotides are bound to the glass by covalent bonds; the compositions which meet said characteristics are referred to in the rest of the specification with the words "microarray", "chip" or "microchip". Among these compositions in the form of microarray, there is a special preference for those which contain more than one copy of each one of the oligonucleotides which form part thereof, very especially preferring that the number of copies of each one of the nucleotides present is at least 12.

[0087] The scope of the invention also includes any diagnostic device which comprises a composition of the invention. The expression "diagnostic device" refers not only to that which serves to determine if the individual suffers from a disease or not but also those which serve to classify the disease an individual is suffering from as belonging to a subtype associated to a determined form of future evolution of said disease and, which therefore, also have a prognostic value of the future evolution of the disease.

[0088] The invention also provides a method for diagnosing a neoplasia originating from hematopoietic cells and/or making a prognosis of the evolution thereof which comprises the in vitro detection from a biological sample and the statistical analysis of the expression level of at least one significant gene for classifying the sample as associated or not to said neoplasia, a gene which is selected from the group composed of GABARAP, NPM3, ABCB1, ABCB4, ABCC3, ABCC5, ABCC6, ABHD1, ABL1, ACTN1, AF1q, AKR1A1, ALDH1A1, ALK, ANK2, ANPEP, ANXA6, ANXA7, APAF1, APEX, ARHGEF2, ARS2, ASNS, ATIC, ATM, ATP5O, BAX, BCL10, BCL2, BCL2A1, BCL2L1, BCL2LAA, BCL3, BCL6, BCL7A, BCL7b, BCR, BECN1, BIK, BIRC3, BIRC5, BLMH, BLR1, BLVRB, BMI1, BMP6, BRMS1, BST2, BTG1, BUB1, C21orf33, C5orf13, CA12, CALD1, CANP2, CASC3, CASP1, CASP3, CASP4, CASP5, CASP6, CASP7, CASP8, CASP9, CAST, CATSD, CBFA2T1, CBFB, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCR6, CCR7, CCT6A, CD14, CD19, CD2, CD22, CD24, CD28, CD33, CD34, CD36, CD38, CD3E, CD4, CD44, CD47, CD48, CD5, CD58, CD59, CD6, CD7, CD79A, CD79B, CD8, CD81, CD83, CD86, CD9, CDA, CDC25A, CDC25B, CDK2, CDK4, CDK5R1, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN3, CDW52, CEBPA, CEBPB, CEBPD, CFL1, CKMT1, CKS2, CML66, COL3A1, COL4A6, CR2, CREB1, CREBBP, CRYAB, CSF2, CSF3, CSRP2, CTGF, CTSB, CUZD1, CXADR, CXCL9, CXCR3, CXCR4, CYC1, CYP1A1, CYP2A6, DAD-1, DAPK1, DCK, DDX6, DEK, DHFR, DLAD, DNAJA1, DNMT3B, DNTT, DOK1, DPF2, DPP4, DRG1, DRP2, E2F1, EB-1, EBI2, EDF1, EEF1A1, EEF1B2, EEF1D, EEF1G, EFNB1, EGFR, EGR1, EIF2B2, EIF3S2, EIF4B, EIF4E, EIF5A, ELF1, ELF4, ENPP1, EphA3, EPOR, ERBB2, ERBB4, ERCC1, ERCC2, ERCC3, ERCC5, ERCC6, ETS1, ETS2, ETV6, ETV7, EZH2, FABP5, FADD, FAIM3, FAM38A, FARP1, FAT, FCER2, FCGR3A, FCGR3B, FGFR1, FGFR3, FGR, FHIT, FKBP9, FLI1, FLJ22169, FLT3, FN1, FNTB, FOS, FUS, G1P2, GABPB2, GATA1, GATA2, GATA3, GCET2, GDI2, GGA3, GJA1, GLUD1, GNL3, GOT1, GRB2, GRIA3, GRK4, GSTP1, GSTT1, GUSB, GZMA, H2AFX, H3F3A, HCK, HELLS, HIF1A, HIST1H2BN, HLA-A, HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB3, HLF, HMMR, HNRPH3, HNRPL, HOXA10, HOXA9, HOXD8, HOXD9, HRAS, HSD17B1, HSPB1, IBSP, ICAM1, ICAM3, ID2, IER3, IFRD1, IGFBP2, IGFBP3, IGFIR, IGLV6-57, IL10, IL15, IL1B, IL2, IL2RA, IL3, IL32, IL3RA, IL4R, IL6, IL6R, IL8, ILF2, IRF1, IRF2, IRF4, IRF8, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, JAK1, JAK2, JUNB, KAI1, KIAA0247, KIAA0864, KIT, KLF1, KLF13, KRAS2, KRT18, LADH, LAG3, LASP1, LCK, LCP1, LEPR, LGALS3, LGALS7, LIF, LIMS1, LMO2, LOC285148, LRP, LSP1, LYL1, LYN, LYZ, MAFB, MAFK, MAGEA1, MAL, MAP3K12, MAP4K1, MAPK10, MAZ, MBP1, MCL1, MCM3, MCM7, MDM2, MEIS1, MEN1, MERTK, MKI67, MLF1, MLF2, MLL, MLLT10, MME, MMP2, MMP7, MMP8, MMP9, MNDA, MPL, MPO, MRPL37, MS4A1, MTCP1, MUC-1, MX1, MYB, MYBL1, MYC, MYOD1, NCALD, NCAM1, NCL, NDP52, NDRG1, NDUFA1, NDUFB, NF1, NFATC1, NFIC, NFKB1, NFIB1A, NINJ1, NPM1, NR3C1, NUMA1, NXF1, ODC1, OGGI, OLIG2, OPRD1, p14ARF, P55CDC, PABPC1, PAX5, PAX6, PAX8, PBX1, PBX3, PCA1, PCD, PCNA, PDCD1, PDGFA, PDGFRB, PDHA1, PGF, PGRMC1, PICALM, PLA2G6, PLAU, PLK1, PLP, PLS3, PLZF, PML, PMM1, POLR2c, POU2F2, PPP1CC, PRAME, PRKCI, PRKCQ, PRKDC, PRL, PRTN3, PSMA5, PSMB4, PSMC5, PSMD7, PTEN, PTGS1, PTHLH, PTK2, PTK2B, PTN, PTPRCCD, PYGB, RAD51, RAF1, RAG1, RARA, RARB, RB1, RBBP4, RBBP6, RBBP8, RBP4, RET, RGS1, RGS1, RIS1, RORA, RPL17, RPL23A, RPL24, RPL36A, RPL37A, RPL41, RPS3, RPS5, RPS9, RUNX1, RxRA, S100A2, S100A8, SDC1, SDHD, SELE, SELL, SEPW1, SERPINA9, SERPINB5, SERPNINA9, SFTPB, SIAT4A, SLC7A5, SNRPB, SOSTDC1, SP1, SPI1, SPN, SPRRIA, SREBF1, SSBP1, STAT1, STAT3, STAT5B, SUMO1, TACSTD2, TAGLN2, TAL1, TBP, TCEB1, TCF1, TCF3, TCF7, TCL1A, TCRbeta, TEGT, TERF1, TERT, TFCP2, TFRC, THBS1, THPO, TIA-2, TIAM1, TK1, TLX1, TMEM4, TNF, TNFRSF10C, TNFRSF1A, TNFRSF25, TNFRSF5, TNFRSF6, TNFRSF8, TNFSF10, TNFSF5, TNFSF6, TOP2A, TOPORS, TP73, TRA@, TRADD, TRAF3, TRAP1, TRIB2, TXNRD1, UBE2C, UHRF1, UVRAG, VCAM1, VEGF, VPREB1, WBSCR20C, WNT16, WTI, XBP1, XPO6, XRCC3, XRCC5, ZAP70, ZFPL1, ZNF42, ZNFN1A1, ZYX, 18S rRNA, 28S rRNA, and whose expression level is determined by the evaluation of the concentration of its corresponding mRNA by the use of at least one probe which has a sequence complementary to a fragment of a strand of said gene, a probe which is selected from the group of oligonucleotides composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563.

[0089] The genes which form part of the aforementioned group are human genes. Therefore, whenever the words "subject" or "individual" are used hereinafter, they will make reference to a human being.

[0090] A particular case of this method is that which comprises an additional previous step of identification of genes significant for the classification of the biological sample analysed as associated or not to a specific type of neoplasia originating from hematopoietic cells, a classification which includes not only the diagnosis of the existence of said neoplasia in the individual from which the sample has been taken, but which may also consist, in additional or alternative form, of the discrimination between specific subtypes of said neoplasia which correspond to different future forms of evolution of said neoplasia this constituting the classification of one or another subtype of the evolution of the neoplasia considered in the future. In this particular case of the method of the invention which comprises a previous step of identification of genes significant for making the desired classification, said previous step comprises the steps of: [0091] a) deciding the possible categories wherein the sample can be classified; [0092] b) obtaining biological samples from individuals which have previously been assigned by a method different to that claimed to any of the possible classification categories, so that there are samples of each one of the possible categories; [0093] c) obtaining the total mRNA of each one of the samples; [0094] d) obtaining the corresponding total cRNA, labelled by a method which allows its subsequent detection, of at least one aliquot of each one of the samples of mRNA, an aliquot whereto is added before the obtainment of the cRNA at least one sequence of polyadenylated nucleotides of low homology with human genes for which it acts as internal positive control of the process; [0095] e) adding to one of the aliquots of cRNA which are going to be used in step f) at least one oligonucleotide of low homology with human genes different from and not complementary to any possible sequence of nucleotides which have been added in step d), for which it acts as positive hybridization control; [0096] f) hybridizing, in strict conditions, at least one aliquot of total cRNA of each one of the samples with at least one microarray which comprises at least two copies of each one of the oligonucleotides from the group composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, a microarray which additionally comprises: [0097] a. at least two points which correspond to different aliquots of the solvent wherein nucleotides are found at the time of their deposit on the surface of the microarray, for which they serve as blank, [0098] b. at least two copies of at least one oligonucleotide for each one of the polyadenylated sequences added in step d), an oligonucleotide whose sequence will correspond to a fragment, different from the polyadenylation zone, of the sequence of polyadenylated nucleotides whose evolution in the process has to be controlled; [0099] c. for each one of the oligonucleotides added in step e), at least two copies of an oligonucleotide complementary thereto; [0100] d. at least two copies of each member of at least one pair of oligonucleotides wherein the sequence of one of the members corresponds to a sequence of zone 5' and the sequence of the other corresponds to a sequence of zone 3' of the mRNA of a gene which is expressed in constitutive form in any cell of hematopoietic origin; [0101] e. at least two copies of at least one oligonucleotide of low homology with human genes different from any of the oligonucleotides defined in section b. and different from any of the synthetic oligonucleotides added optionally in step e); [0102] g) detecting and quantifying the signal of cRNA hybridized with each one of the copies of each one of the oligonucleotides present in the microarray, as well as the signal corresponding to the points of the solvent; [0103] h) calculating the average level of intensity of hybridization of each one of the oligonucleotides of the microarray calculating the average of the intensities of the copies of each one of the oligonucleotides; [0104] i) taking the hybridization as valid if the following conditions are complied with: [0105] a. the ratio between the average intensity and the average background of all the oligonucleotides of the microarray is greater than 10; [0106] b. the value of the average coefficient of variation of all the replicas of oligonucleotides should be less than 0.3; [0107] c. the average value of negative control should be less than 2.5 times the average value of the points corresponding to the solvent; [0108] d. there is a signal both in the hybridization controls and in the internal positive controls used as process control; [0109] j) normalizing the data; [0110] k) eliminating the oligonucleotides with values of average intensity minus average background noise less than approximately 2 times the average value obtained with the points corresponding to the solvent, as well as the oligonucleotides with an interquartile range of normalized intensity throughout the samples less than 0.3; [0111] l) performing the statistical analysis to find the statistically significant oligonucleotides to differentiate between the different categories and be able to classify a sample which has not been previously assigned to any category, choosing said oligonucleotides among those which have not been eliminated in the previous steps, until obtaining "n" oligonucleotides which either have a value of p less than a limit which is chosen from the open range of 0 to 0.05, preferably using for it a method with capacity to reduce false positives, or that which best defines the category established; [0112] m) checking that the grouping of the samples according to the differences in intensities between the different samples detected for the statistically significant oligonucleotides gives rise to the samples being classified in the same categories as those which had previously been assigned by a different method.

[0113] It is preferred that the average value calculated in section h) is the trimmed mean, for which reason it is preferable that the microarray comprises at least four copies of each one of the oligonucleotides present therein.

[0114] The normalization can be carried out with different methods. There is preference for the use of functions contained in access packages freely accessed over the Internet designed for the processing, calculation and graphic representation of data, such as the packages designed in R programming language, available to download from CRAN (http://cran.r-project.org/) or Bioconductor (http://www.bioconductor.orq). The "variance stabilization normalization" method available in the "vsn" package in R.

[0115] The identification of the statistically significant oligonucleotides to differentiate between the different categories can be carried out using different methods, having preference for those wherein a value p is determined that determines the threshold of probability under which all the genes whose expression difference has a value less than p would be considered significant and, among these, those which have the capacity to carry out corrections on the value of p, such as, among others, Bonferroni's method or Welch's test. The value of p will be chosen from the open range of 0 to 0.05, preferring, when possible, a value of p close to 0.001 and with correction, it being possible to increase said value at maximum to 0.05 (value which is not included among those possible) until which statistically significant oligonucleotides are found to differentiate between the categories among which one wants to classify the samples. A possibility for carrying out these calculations is, again, the use of functions contained in packages freely accessed over the Internet designed for the processing, calculation and graphic representation of data. In particular, the mt.maxT function of the multtest package in R can be used for the identification of the statistically significant oligonucleotides.

[0116] Another possibility for the identification of statistically significant oligonucleotides to be able to differentiate between the categories of established samples is the use of the "nearest shrunken centroids" method, a variation of the "nearest centroids" method (Tibshirani et al., 2002), which identifies a group of genes which best characterizes a predefined class and uses this group of genes to predict the class which new samples belong to. To do this, again functions contained in packages freely accessed over the internet may be resorted to, such as the "pam.sup.a" package in R, wherein it is possible to find functions to carry out the so-called "Prediction Analysis for Microarrays (PAM)", which makes use of the "nearest shrunken centroids" method.

[0117] After identifying the statistically significant genes to distinguish between categories of samples established from the corresponding oligonucleotides, they can be used for classifying new samples due to similarity between the expression profile of those genes in the sample analysed and those corresponding to each one of the classification categories. Alternatively, when there are only 2 possible classification categories (which will be normal when one wants to diagnose the presence or absence of a certain type of leukaemia in an individual), it is possible to obtain a mathematical function of classification of samples which determine the probability "p.sub.i" of a sample "i" belonging to one category or another. To do this, a subunit of the samples is chosen which have been previously assigned to each one of the possible categories by a method different to that of the invention and the value of 0 is arbitrarily associated to each one of the samples of one of the categories "a" (typically, the category of "not" associated to the leukemia one wants to diagnose") of belonging to the other possible category, whilst each one of the samples of the subunit belonging to the other possible category "b" (typically, the category of "associated" to the leukemia one wants to diagnose") arbitrarily receives the value "1" for its probability of belonging to its own category. With this, logistical regression is used to calculate, with the aid of the probability values assigned to each one of the samples and the values of normalized trimmed mean intensity obtained for each one of the samples with each one of the "n" oligonucleotides which has been identified as a statistically significant oligonucleotide in the previous step, coefficients for each one of said oligonucleotides which make it possible to obtain a function of probability p.sub.i of a sample "i" belonging to category "b", a function which will be of the type

p.sub.i=1/(1+e.sup.-xi)

and which results from the algebraic transformation of the expression which equals Neperian logarithm of the quotient between the probability of an event occurring and the probability that it does not occur at a function x.sub.i which includes as variables each one of the factors which may influence the event, i.e.

ln p 1 - p = x i ##EQU00001##

function x.sub.i which, in the present case, will depend on the intensity values obtained for each one of the statistically significant oligonucleotides and which responds to an expression of the type:

x i = constant + m = 1 n ( coeff_olig m * lmn i _olig m ) ##EQU00002##

where [0118] coeff_olig.sub.m represents the coefficient calculated for a specific oligonucleotide "m" [0119] Imn.sub.i.sub.--olig.sub.m represents the average value of normalized intensity obtained in the hybridization of the sample i calculated for the oligonucleotide "m" [0120] "m" varies from 1 to "n" [0121] n is the total number of oligonucleotides considered significant.

[0122] The function p.sub.i obtained after calculating by logistical regression the coefficient corresponding to each oligonucleotide permits classifying a sample "i" as belonging to one or another category, considering that the values of p.sub.i over 0.5 (and which will be less than or equal to 0) indicate that the sample belongs to category "b", whilst the values of p.sub.i less than 0.5 indicate that the sample belongs to category "a". Said function p.sub.i will be considered valid if, on being applied to the samples wherefrom it has been deduced, it is capable of classifying them correctly and, furthermore, as it is applied to the subgroup of samples which have not been taken into account to deduce the function, but whose category is known as it has been previously assigned by a method other than that of the invention, it is also capable of classifying them correctly.

[0123] Alternatively, when the identification of the statistically significant genes has been performed using the "Prediction Analysis for Microarrays" method, the classifier can be obtained with the corresponding functions of the "pamr.sup.a" package in R, which also starts from the assignment of the value of probability 0 to a subgroup of members of one of the categories and the value of probability 1 to a subgroup of the members of the other category. Again, the calculation of coefficients for statistically significant oligonucleotides permits the calculation of values of probability of belonging to one or another category, also considering that the values over 0.5 indicate belonging to the category whose members are arbitrarily assigned value 1 and the values less than 0.5 indicate belonging to the other category.

[0124] A particular case of the method of the invention is that wherein one wants to classify samples as associated or not to a type of leukemia. In that case, blood samples are preferred, especially those of peripheral blood, as biological samples to carry out in vitro the method of the invention.

[0125] Once the statistically significant genes have been identified to associate a determined type of neoplasia as originating from hematopoietic cells, the method of the invention can be used for classifying samples according to the expression level of said genes in said samples. The neoplasia can be, for example, a specific type of leukemia. A particular case of this embodiment of the method of the invention is constituted by the association of chronic lymphatic leukemia, thus allowing the diagnosis of this disease by the method of the invention. To do this, significant genes are considered to be those genes whose expression level is analysed on applying the method of the invention at least those of the group of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1 and the analysis is carried out on blood samples. The method can be additionally applied including the analysis of the expression level of at least genes IRF8 and COL3A1. Preferably, the analysis of the expression level of these genes is carried out by evaluating the level of their corresponding mRNA by hybridization of their corresponding cRNA with oligonucleotides SG117, SG428, SG459, SG507, SG508, SG461 and SG493, which are preferred to be associated to a solid support forming part of a microarray. When the evaluation of the hybridized cRNA with each one of those oligonucleotides is carried out thanks to the prior labelling of the cRNA with biotin, the staining of the microarray hybridized with streptavidin conjugated with a fluorophore and the detection of the signal emitted by said fluorophore, it is preferred that the fluorophore is Cy3, which permits diagnosing the presence of CLL in the subject from which the sample has been taken by the classification of sample "i" analysed as associated to CLL from the calculation of the probability that said sample is associated to CLL from the formula p.sub.i=1/(1+e.sup.-x.sup.i), wherein x.sub.i is calculated by the formula

x.sub.i=-719.241486+(2.44756372*Imn.sub.i.sub.--CD79A)+(7.38657611*Imn.s- ub.i.sub.--FAIM3)+(23.1465464*Imn.sub.i.sub.--HLA-DRA)+(43.6287742*Imn.sub- .i.sub.--IRF8)-(19.3978182*Imn.sub.i.sub.--COL3A1)-(2.80282646*Imn.sub.i.s- ub.--HLA-DRB3)+(49.5345672*Imn.sub.i.sub.--HLA-DQA1) [0126] formula wherein each one of the values denominated with the abbreviation "Imn.sub.i" followed by the abbreviation of a gene makes reference to the average value of normalized intensity obtained after detecting the hybridization signal corresponding to the oligonucleotide which is being used as probe to evaluate the expression of the said gene and which permits classifying the subject as subject not suffering from CLL if the value of p.sub.i is less than 0.5 and as subject suffering from CLL if the value of p.sub.i is greater than 0.5. Alternatively, significant genes can be considered as those whose expression level is analysed on applying the method of the invention for the diagnosis of CLL at least those of the group of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, additionally including the analysis of the expression level of at least gene CDW52. Preferably, the analysis of the expression level of these genes is carried out by evaluating the level of its corresponding mRNA by hybridization of its corresponding cRNA with oligonucleotides SG117, SG428, SG459, SG507, SG508 and SG237, which it is preferred are associated to a solid support forming part of a microarray.

[0127] Another particular case of the application of the method of the invention for classifying samples as associated to a specific type of leukemia according to the expression level in said samples of statistically significant genes constitutes the classification of a sample as associated to a specific subtype of chronic lymphatic leukemia, "stable" CLL or "progressive" CLL, which makes it possible that the method of the invention serves to make a prognosis for the future evolution of subjects which have been diagnosed with CLL. When the samples analysed are of peripheral blood, the genes considered statistically significant to perform the classification of the samples are at least genes PSMB4, FCER2 and POU2F2, it being possible to additionally analyse the expression level of at least one gene selecting the group composed of ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4 or the totality thereof.

[0128] An additional aspect of the invention is the use of devices to evaluate the expression level of at least one of the genes of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4, CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 with the aim of diagnosing the presence of CLL in an individual and/or making a prognosis of his/her evolution. A particular case of this aspect of the invention is the use of devices of evaluation of the expression level of at least one gene of the group composed of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 for the diagnosis of the presence of CLL in an individual, wherein it is preferred that the device evaluates at least the expression level of genes CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, it being possible for the device to evaluate, additionally, the expression level of at least genes IRF8 and COL3A1 or at least gene CDW52. Another particular case of this aspect of the invention is the use of devices of evaluation of the expression level of at least one gene of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4, CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 to make a prognosis of the future evolution of CLL in an individual.

DETAILED DESCRIPTION OF THE INVENTION

Design of the Microarray Device

Genes Included in the Microarray

[0129] A revision was performed of the scientific literature and genes were selected due to their special involvement in the biology of blood cells or in the pathology of the different neoplasias The genes selected can be included within these 4 large groups:

a) With an Important Role in the Biology of the Hematopoietic Cells:

[0130] Genes whose protein is expressed or repressed in the different steps through which these cells pass in their differentiation to mature forms. [0131] Genes whose protein is specifically expressed in accordance with the line whereto the cell belongs. [0132] Genes which code adhesion molecules

b) Involved in Different Types of Hematological Neoplasias:

[0132] [0133] Genes whose expression (a level of mRNA or protein) is altered in different types of neoplasias, or associated to resistance to chemotherapy

c) Cancer-Related:

[0133] [0134] Genes which code proteins associated with proliferation, metastasis or genes whose expression is increased in a large number of tumours.

d) Described in Publications Related to Neoplasias:

[0134] [0135] Genes which, without having a special ratio with hematological neoplasias or blood cell biology, have appeared in the scientific literature as statistically associated to a type of neoplasia

[0136] The characteristics of the genes can be consulted, for example, in: www.ncbi.nlm.nih.qov/Genbank, selecting the "Gene" option in the drop-down menu which appears and entering the corresponding identification number (GenID) in the GenBank. The genes whose expression can be analysed with the microarray, their corresponding identification number in the GenBank, as well as the oligonucleotides present in the microarray to be used as probes to analyse the expression of said genes appear below in Table 1.

Probes of Oligonucleotides which Represent Each Gene.

[0137] For each one of the 534 genes related to hematological neoplasias, as well as for the genes corresponding to .beta.-actin, glyceraldehyde-3-phosphate dehydrogenase, 18S rRNA and 28S rRNA, the mrRNA sequence is sought in GenBank (www.ncbi.hlm.nih.gov/Genbank/). An oligonucleotide is designed (probe) from the GenBank sequence, specific for each one of the genes selected. In some genes several oligonucleotides were designed situated in zones 5' and 3' of the gene, in order to analyse the integrity of the mRNA.

[0138] To ensure specificity in the design of the probes, the following criteria were taken into consideration: [0139] Length of the probe to guarantee that all the probes are going to have a similar behaviour, [0140] GC content of the probe between 40 and 60%. This characteristic is also taken into consideration to ensure that all the probes are going to have a similar behaviour. [0141] Localization in the gene. Probes localized at least 3000 nucleotides from 3' (poly(A)) of the selected mRNA sequence were localized. [0142] Sense of the probe. A strand was chosen with "sense", i.e. the sequences of the oligonucleotides coincide with sequences of fragments of the corresponding mRNA, instead of being sequences complementary to said fragments. This decision involves that the labelled genetic material has to be antisense (complementary to sense). [0143] Specificity of the probe. To avoid non-specific hybridization, probes were selected which have a percentage of homology, calculated by the BLAST tool (available on the website http://www.ncbi.nlm.nih.gov/), less than 70%.

[0144] The data on the oligonucleotides used as probes, the identification number of its corresponding sequence in the attached list, as well as data (identification number in GenBank, usual abbreviation and name) of the genes for the detection of whose expression said oligonucleotides have been designed, are shown below in the Table 1.

TABLE-US-00001 TABLE 1 Oligonucleotides used as probes to detect the expression of human genes Oligo- Usual nucleotide SEQ ID NO: GenID abbreviation Description SG1 SEQ ID 11337 GABARAP Protein associated to the GABA receptor NO: 1 SG2 SEQ ID 28778 IGLV6-57 Variable lambda immunoglobulin 6-57 NO: 2 SG3 SEQ ID 5092 PCD 6-pyruvoyl-tetrahydropterine NO: 3 synthase/dimerization cofactor of the nuclear factor of 1 alpha hepatocytes (TCF1) SG4 SEQ ID 83988 NCALD delta neurocalcin NO: 4 SG5 SEQ ID 58511 DLAD deoxyribonuclease II beta NO: 5 SG6 SEQ ID 25928 SOSTDC1 which contains a sclerostin 1 domain NO: 6 SG7 SEQ ID 10630 TIA-2 glycoprotein associated to the lung cell NO: 7 membrane, type I SG8 SEQ ID 5834 PYGB phosphorylase, glycogen; brain NO: 8 SG9 SEQ ID 3987 LIMS1 with domains LIM and similar to the antigen NO: 9 of senescent cells 1 SG10 SEQ ID 25 ABL1 homologue to the viral oncogene of Abelson NO: 10 v-abl 1 murine leukemia SG11 SEQ ID 4733 DRG1 GTP-binding protein regulated by NO: 11 development 1 SG12 SEQ ID 25855 BRMS1 Metastasis suppressor of breast cancer 1 NO: 12 SG13 SEQ ID 84696 ABHD1 which contains an abhydrolase 1 domain NO: 13 SG14 SEQ ID 3475 IFRD1 Development regulator related to interferon 1 NO: 14 SG15 SEQ ID 6173 RPL36A Ribosomal protein L36a NO: 15 SG16 SEQ ID 3485 IGFBP2 Binding protein to the growth factor similar NO: 16 to insulin 2, 36 kDa SG17 SEQ ID 10397 NDRG1 Gene regulated downstream by N-myc 1 NO: 17 SG18 SEQ ID 11328 FKBP9 FK506 9-binding protein, 63 kDa NO: 18 SG19 SEQ ID 10241 NDP52 protein of the nuclear domain 10 NO: 19 SG20 SEQ ID 2171 FABP5 protein which binds to fatty acids 5 NO: 20 (associated to psoriasis) SG21 SEQ ID 10160 FARP1 protein with FERM, RhoGEF (ARHGEF) NO: 21 and pleckstrin 1 domains (derived from chrondrocytes) SG22 SEQ ID 5228 PGF Placental growth factor, protein related to NO: 22 the endothelial growth factor SG23 SEQ ID 2665 GDI2 GDP 2 dissociation inhibitor NO: 23 SG24 SEQ ID 8407 TAGLN2 transgelin 2 NO: 24 SG25 SEQ ID 645 BLVRB biliverdin reductase B (flavin reductase NO: 25 (NADPH)) SG26 SEQ ID 5692 PSMB4 subunit of proteasome (prosome, NO: 26 macropain), beta-type, 4 SG27 SEQ ID 4070 TACSTD2 transducer of the calcium signal associated NO: 27 to tumours 2 SG28 SEQ ID 6921 TCEB1 Elongation factor of transcription B (SIII), NO: 28 polypeptide 1 (15 kDa, elongin C) SG29 SEQ ID 1915 EEF1A1 elongation factor in the eukaryotic NO: 29 translation 1 alpha 1 SG30 SEQ ID 3020 H3F3A histone H3, family 3A NO: 30 SG31 SEQ ID 4953 ODC1 ornithine decarboxylase 1 NO: 31 SG32 SEQ ID 7520 XRCC5 Of repair of X rays which complement the NO: 32 defective repair in Chinese hamster cells 5 (reconnection of breakages in the double helix; autoantigen Ku, 80 kDa) SG33 SEQ ID 3486 IGFBP3 binding protein to growth factor similar to NO: 33 insulin 3 SG34 SEQ ID 4691 NCL nucleolin NO: 34 SG35 SEQ ID 6273 S100A2 calcium S100 A2-binding protein NO: 35 SG36 SEQ ID 6152 RPL24 ribosomal protein L24 NO: 36 SG37 SEQ ID 2697 GJA1 Bone filling protein, alpha 1, 43 kDa NO: 37 (connexin 43) SG38 SEQ ID 2990 GUSB glucuronidase, beta NO: 38 SG39 SEQ ID 3292 HSD17B1 hydroxysteroid (17-beta) dehydrogenase 1 NO: 39 SG40 SEQ ID 6439 SFTPB surfactant protein, associated to lung B NO: 40 SG41 SEQ ID 6147 RPL23A ribosomal protein L23a NO: 41 SG42 SEQ ID 1466 CSRP2 protein rich in cysteine and glycine 2 NO: 42 SG43 SEQ ID 1525 CXADR receptor of the coxsackie virus and NO: 43 adenovirus SG44 SEQ ID 1937 EEF1G elongation factor of eukartyotic 1 gamma NO: 44 elongation SG45 SEQ ID 1164 CKS2 subunit regulating the kinase CDC28 2 NO: 45 protein SG46 SEQ ID 1288 COL4A6 collagen, type IV, alpha 6 NO: 46 SG47 SEQ ID 1410 CRYAB crystalline, alpha B NO: 47 SG48 SEQ ID 1537 CYC1 cytochrome c-1 NO: 48 SG49 SEQ ID 2342 FNTB farnesyltransferase, CAAX box, beta NO: 49 SG50 SEQ ID 2805 GOT1 glutamic-oxaloacetic transaminase 1, NO: 50 soluble (aminotransferase 1 aspartate) SG51 SEQ ID 3963 LGALS7 Lectin, which binds to galactosides, soluble, NO: 51 7 (galectin 7) SG52 SEQ ID 5268 SERPINB5 Serine (or cysteine) inhibitor proteinase, NO: 52 clade B (ovalbumin, member 5 SG53 SEQ ID 5705 PSMC5 Subunit of proteasome (prosome, NO: 53 macropain) 26S, ATPase, 5 SG54 SEQ ID 5764 PTN pleiotrophin (growth factor of bonding to NO: 54 heparin 8, growth promoter factor of neurites 1) SG55 SEQ ID 5932 RBBP8 Retinoblastoma 8-binding protein NO: 55 SG56 SEQ ID 5996 RGS1 Regulator of the signalling by proteins G 1 NO: 56 SG57 SEQ ID 6256 RXRA Retinoid X receptor, alpha NO: 57 SG58 SEQ ID 6392 SDHD succinate dehydrogenase complex, subunit NO: 58 D, integral membrane protein SG59 SEQ ID 6415 SEPW1 selenoprotein W, 1 NO: 59 SG60 SEQ ID 6742 SSBP1 binding protein to single-strand DNA 1 NO: 60 SG61 SEQ ID 7009 TEGT transcript of gene increased in the testicle NO: 61 (BAX 1 inhibitor) SG62 SEQ ID 8341 HIST1H2BN histone 1, H2bn NO: 62 SG63 SEQ ID 8678 BECN1 beclin 1 (protein similar to myosin which NO: 63 interacts with BCL2, of twisted helix) SG64 SEQ ID 310 ANXA7 annexin A7 NO: 64 SG65 SEQ ID 4694 NDUFA1 Alpha subcomplex of NADH NO: 65 dehydrogenase (ubiquinone) 1, 1, SG66 SEQ ID 9181 ARHGEF2 guanine rho/rac exchange factor (GEF) 2 NO: 66 SG67 SEQ ID 9315 C5orfl3 Open reading frame 13 of chromosome 5 NO: 67 SG68 SEQ ID 7494 XBP1 X 1 box-binding protein NO: 68 SG69 SEQ ID 9636 G1P2 protein inducible by the alpha interferon NO: 69 (clone IFI-15K) SG70 SEQ ID 2746 GLUD1 glutamate dehydrogenase 1 NO: 70 SG71 SEQ ID 6273 S100A2 calcium S100 A2-binding protein NO: 71 SG72 SEQ ID 3927 LASP1 LIM and SH3 1 protein NO: 72 SG73 SEQ ID 10630 TIA-2 glycoprotein associated to the lung cell NO: 73 membrane type I SG74 SEQ ID 10857 PGRMC1 Membrane component of the progesterone NO: 74 1 receptor SG75 SEQ ID 7542 ZFPL1 protein similar to that of zinc finger 1 NO: 75 SG76 SEQ ID 11184 MAP4K1 Kinase protein activated by mitogens 1 NO: 76 SG77 SEQ ID 6772 STAT1 Signal transducer and transcription activator NO: 77 1, 91 kDa SG78 SEQ ID 3189 HNRPH3 Heterogeneous nuclear ribonucleoprotein NO: 78 H3 (2H9) SG79 SEQ ID 10330 TMEM4 Transmembrane protein 4 NO: 79 SG80 SEQ ID 9766 KIAA0247 KIAA0247 NO: 80 SG81 SEQ ID 25907 RIS1 of senescence induced by Ras 1 NO: 81 SG82 SEQ ID 51593 ARS2 Arsenate-resistant protein ARS2 NO: 82 SG83 SEQ ID 771 CA12 Carbonic anhydrase XII NO: 83 SG84 SEQ ID 1933 EEF1B2 elongation factor of the eukaryotic 1 beta 2 NO: 84 translation SG85 SEQ ID 28951 TRIB2 homologue to tribbles 2 (Drosophila) NO: 85 SG86 SEQ ID 79065 FLJ22169 similar to that of autophagy 9 APG9 1 (S. cerevisiae) NO: 86 SG87 SEQ ID 440 ASNS asparagine synthetase NO: 87 SG88 SEQ ID 260294 WBSCR20C Chromosome region 20C of Williams NO: 88 Beuren syndrome SG89 SEQ ID 10327 AKR1A1 member A1 of the aldo-keto reductase 1 NO: 89 family (aldehyde reductase) SG90 SEQ ID 6698 SPRR1A Small proline 1A-rich protein NO: 90 SG91 SEQ ID 1947 EFNB1 ephrin-B1 NO: 91 SG92 SEQ ID 6193 RPS5 ribosomal protein S5 NO: 92 SG93 SEQ ID 6203 RPS9 ribosomal protein S9 NO: 93 SG94 SEQ ID 6139 RPL17 ribosomal protein L17 NO: 94 SG95 SEQ ID 2114 ETS2 homologue to oncogene E26 of the NO: 95 erythroblastosis virus v-ets 2 (avian) SG96 SEQ ID 1975 EIF4B initiation factor of the eukaryotic translation NO: 96 4B SG97 SEQ ID 7791 ZYX Zyxin NO: 97 SG98 SEQ ID 23214 XPO6 exportin 6 NO: 98 SG99 SEQ ID 285148 LOC285148 Hypothetical protein LOC285148 NO: 99 SG100 SEQ ID 8209 C21orf33 open reading frame 33 of chromosome 21 NO: 100 SG101 SEQ ID 1936 EEF1D elongation factor of the eukaryotic NO: 101 translation 1 delta (guanine nucleotide exchange protein) SG102 SEQ ID 26986 PABPC1 poly(A)-binding protein, cytoplasmic 1 NO: 102 SG103 SEQ ID 5930 RBBP6 retinoblastoma 6-binding protein NO: 103 SG104 SEQ ID 3265 HRAS homologue to the viral oncogene of the NO: 104 Harvey v-Ha-ras rat sarcoma SG105 SEQ ID 23163 GGA3 ARF-binding protein, which contains NO: 105 gamma-adaptin, associated to golgi SG106 SEQ ID 1072 CFL1 cophilin 1 (non-muscular) NO: 106 SG107 SEQ ID 8668 EIF3S2 initiation factor of the eukaryotic translation NO: 107 3, subunit 2 beta, 36 kDa SG108 SEQ ID 3875 KRT18 keratine 18 NO: 108 SG109 SEQ ID 3480 IGFIR growth factor receptor similar to insulin 1 NO: 109 SG110 SEQ ID 3576 IL8 Interleukin 8 NO: 110 SG111 SEQ ID 3659 IRF1 Interferon regulating factor 1 NO: 111 SG112 SEQ ID 3660 IRF2 Interferon regulating factor 2 NO: 112 SG113 SEQ ID 4067 LYN Homologue to the oncogene related to the NO: 113 viral sarcoma of Yamaguchi V-yes-1 SG114 SEQ ID 4069 LYZ Lysozyme (renal amiloidosis) NO: 114 SG115 SEQ ID 4792 NFKB1A Nuclear factor of the gene enhancer of the NO: 115 kappa light polypeptide in B L-lymphocytes (p105) SG116 SEQ ID 4150 MAZ Zinc finger protein associated to MYC NO: 116 (transcription factor of binding to purins) SG117 SEQ ID 973 CD79A Antigen CD79A (associated to alpha NO: 117 immunoglobulins) SG118 SEQ ID 4172 MCM3 Deficient maintenance of minichromosomes

NO: 118 (S. cerevisiae) 3 SG119 SEQ ID 421 MEIS1 Homologue to Meis1 (mouse) NO: 119 SG120 SEQ ID 5657 PRTN3 Proteinase 3 (serine proteinase, NO: 120 autoantigen of Wegener's granulomatosis of neutrophils) SG121 SEQ ID 4313 MMP2 Metalloproteinase of matrix 2 (gelatinase A, NO: 121 72 kD gelatinase of, 72 kD collagenase type IV) SG122 SEQ ID 4316 MMP7 Metalloproteinase of matrix 7 (matrilysin, NO: 122 uterine) SG123 SEQ ID 4317 MMP8 Metalloproteinase of matrix 8 (neutrophil NO: 123 collagenase) SG124 SEQ ID 1796 DOK1 Adapter protein 1, 62 kD (downstream NO: 124 respect to thyrosine kinase 1) SG125 SEQ ID 5154 PDGFA Alpha polypeptide of the platelet-derived NO: 125 growth factor SG126 SEQ ID 5617 PRL Prolactin NO: 126 SG127 SEQ ID 5894 RAF1 Homologue to the viral oncogene of murine NO: 127 leukemia V-raf-1 1 SG128 SEQ ID 5915 RARB Retinoic acid receptor, beta NO: 128 SG129 SEQ ID 4985 OPRD1 Opioid receptor, delta 1 NO: 129 SG130 SEQ ID 5979 RET proto-oncogene ret (multiple endocrine NO: 130 neoplasia and medullary thyroid carcinoma 1, Hirschsprung's disease) SG131 SEQ ID 6720 SREBF1 Transcription factor of binding to sterol NO: 131 regulatory elements 1 SG132 SEQ ID 7124 TNF Tumour necrosing factor (TNF superfamily, NO: 132 member 2) SG133 SEQ ID 7013 TERF1 Binding factor to telomeric repetitions NO: 133 (which interact with NIMA) 1 SG134 SEQ ID 7412 VCAM1 Molecule of adhesion to vascular cells 1 NO: 134 SG135 SEQ ID 539 ATP5O ATP synthase, H+ carrier, mitochondrial F1 NO: 135 complex, subunit O (protein which gives sensitivity to oligomycin) SG136 SEQ ID 959 TNFSF5 Tumour necrosing factor (ligand) NO: 136 superfamily, member 5 (hyper-IgM syndrome) SG137 SEQ ID 5432 POLR2C Polypeptide C (directed at DNA) of the RNA NO: 137 polymerase II (33 kD) SG138 SEQ ID 8398 PLA2G6 Phospholipase A2, group VI (cytosolic, NO: 138 calcium-dependent) SG139 SEQ ID 908 CCT6A TCP1 which contains chaperonin, subunit NO: 139 6A (zeta 1) SG140 SEQ ID 5160 PDHA1 Pyruvate dehydrogenase (lipoamide) alpha 1 NO: 140 SG141 SEQ ID 3939 LADH Lactate dehydrogenase A NO: 141 SG142 SEQ ID 6628 SNRPB Polypeptides B and B1 of the small nuclear NO: 142 ribonucleoprotein SG143 SEQ ID 6628 SNRPB Polypeptides B and B1 of the small nuclear NO: 143 ribonucleoprotein SG144 SEQ ID 3014 H2AFX Histone family H2A, member X NO: 144 SG145 SEQ ID 51253 MRPL37 Mitochondrial ribosomal protein L37 NO: 145 SG146 SEQ ID 11065 UBE2C Enzyme which conjugates with ubiquin E2C NO: 146 SG147 SEQ ID 6188 RPS3 Ribosomal protein S3A NO: 147 SG148 SEQ ID 216 ALDH1A1 Aldehyde dehydrogenase 1 family, member NO: 148 A1 SG149 SEQ ID 10962 AF1q Lymphoid/myeloid or leukemia or of mixed NO: 149 line (homologue to trithorax, Drosophila); translocated to 11 SG150 SEQ ID 861 RUNX1 Runt 1-related transcription (acute myeloid NO: 150 leukemia 1; oncogene aml1) SG151 SEQ ID 4603 MYBL1 Similar to the homologue of the viral NO: 151 oncogene of avian myeloblastisis V-myb 1 SG152 SEQ ID 309 ANXA6 Annexin A6 NO: 152 SG153 SEQ ID 238 ALK Anaplastic lymphoma kinase (Ki-1) NO: 153 SG154 SEQ ID 4332 MNDA Antigen for nuclear differentiation myeloid NO: 154 cells SG155 SEQ ID 317 APAF1 Apoptotic protease activator factor NO: 155 SG156 SEQ ID 330 BIRC3 which contains IAP repetitions of NO: 156 baculovirus 3 SG157 SEQ ID 368 ABCC6 ATP-binding module, subfamily C NO: 157 (CFTR/MRP), member 6 SG158 SEQ ID 471 ATIC 5-aminoimidazol-4-carboxamide NO: 158 ribonucleotide formyltransferase/IMP cyclohydrolase SG159 SEQ ID 472 ATM Mutated ataxia-telangiectasia (includes NO: 159 complementary groups A, C and D) SG160 SEQ ID 581 BAX protein X associated to BCL2 NO: 160 SG161 SEQ ID 595 CCND1 Cyclin D1 (PRAD1: parathyroidal NO: 161 adenomatosis 1) SG162 SEQ ID 596 BCL2 CLL/lymphoma of B 2 lymphocytes NO: 162 SG163 SEQ ID 602 BCL3 CLL/lymphoma of B 3 lymphocytes NO: 163 SG164 SEQ ID 604 BCL6 CLL/lymphoma of B 6 lymphocytes (protein NO: 164 with zinc fingers 51) SG165 SEQ ID 605 BCL7A CLL/lymphoma of B 7A lymphocytes NO: 165 SG166 SEQ ID 9275 BCL7b CLL/lymphoma of B 7B lymphocytes NO: 166 SG167 SEQ ID 8915 BCL10 CLL/lymphoma of B 10 lymphocytes NO: 167 SG168 SEQ ID 598 BCL2L1 similar to BCL2 1 NO: 168 SG169 SEQ ID 613 BCR Grouping breaking point region NO: 169 SG170 SEQ ID 613 BCR Grouping breaking point region NO: 170 SG171 SEQ ID 10215 OLIG2 Transcription factor of oligodendrocytes 2 NO: 171 line SG172 SEQ ID 638 BIK Mortal factor which interacts with BCL2 NO: 172 (apoptosis inducer) SG173 SEQ ID 10018 BCL2LAA Similar to BCL2 (which facilitates NO: 173 apoptosis) SG174 SEQ ID 648 BMI1 Homologue to the viral oncogene of murine NO: 174 leukemia (bmi-1) SG175 SEQ ID 642 BLMH bleomycin hydrolase NO: 175 SG176 SEQ ID 643 BLR1 Burkitt 1 lymphoma receptor, GTP-binding NO: 176 protein SG177 SEQ ID 3381 IBSP Integrin-binding sialoprotein (bone NO: 177 sialoprotein bone sialoprotein II) SG178 SEQ ID 694 BTG1 Gene of translocation of B lymphocytes, NO: 178 anti-proliferative SG179 SEQ ID 699 BUB1 Disinhibited budding by benzimidazoles 1 NO: 179 (homologue of yeasts) SG180 SEQ ID 25 ABL1 homologue to the viral oncogene of that of NO: 180 Abelson's murine leukemia v-abl 1 SG181 SEQ ID 834 CASP1 caspase 1, apoptosis-related cysteine NO: 181 protease (interleukin 1, beta, convertase) SG182 SEQ ID 836 CASP3 caspase 3, apoptosis-related cysteine NO: 182 protease SG183 SEQ ID 837 CASP4 caspase 4, apoptosis-related cysteine NO: 183 protease SG184 SEQ ID 838 CASP5 caspase 5, apoptosis-related cysteine NO: 184 protease SG185 SEQ ID 839 CASP6 caspase 6, apoptosis-related cysteine NO: 185 protease SG186 SEQ ID 840 CASP7 caspase 7, apoptosis-related cysteine NO: 186 protease SG187 SEQ ID 841 CASP8 caspase 8, apoptosis-related cysteine NO: 187 protease SG188 SEQ ID 842 CASP9 caspase 9, apoptosis-related cysteine NO: 188 protease SG189 SEQ ID 865 CBFB Nucleus binding factor, beta subunit NO: 189 SG190 SEQ ID 800 CALD1 Caldesmon 1 NO: 190 SG191 SEQ ID 831 CAST Calpastatin NO: 191 SG192 SEQ ID 993 CDC25A Cell division cycle 25A NO: 192 SG193 SEQ ID 994 CDC25B Cell division cycle 25B NO: 193 SG194 SEQ ID 914 CD2 Antigen CD2 (p50), sheep red blood cell NO: 194 receptor SG195 SEQ ID 916 CD3E Antigen CD3E, epilson polypeptide NO: 195 (complex TiT3) SG196 SEQ ID 920 CD4 Antigen CD4 (p55) NO: 196 SG197 SEQ ID 921 CD5 Antigen CD5 (p56-62) NO: 197 SG198 SEQ ID 923 CD6 Antigen CD6 NO: 198 SG199 SEQ ID 924 CD7 Antigen CD7 (p41) NO: 199 SG200 SEQ ID 925 CD8 Antigen CD8, alpha polypeptide(p32) NO: 200 SG201 SEQ ID 928 CD9 Antigen CD9 (p24) NO: 201 SG202 SEQ ID 4311 MME Membrane metalloendopeptidase (neutral NO: 202 endopeptidase, encephalinase, CALLA, CD10) SG203 SEQ ID 3683 ITGAL Integrin, alpha L (antigen CD11A (p180), NO: 203 antigen associated to the function of lymphocytes 1; alpha polypeptide) SG204 SEQ ID 3684 ITGAM Integrin, alpha M (complement 3 NO: 204 component receptor, alpha; also known as CD11b (p170), polypeptide of the macrophage alpha antigen) SG205 SEQ ID 3687 ITGAX Integrin, alpha X (antigen CD11C (p150), NO: 205 alpha polypeptide) SG206 SEQ ID 90 ANPEP Alanyl-(membrane)aminopeptidase NO: 206 (aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150) SG207 SEQ ID 929 CD14 Antigen CD14 NO: 207 SG208 SEQ ID 6401 SELE Selectin E (endothelial adhesion molecule NO: 208 1) SG209 SEQ ID 2214 FCGR3A Low-affinity receptor IIIa for the Fc fragment NO: 209 of IgG (CD16) SG210 SEQ ID 2215 FCGR3B Low-affinity receptor IIIb for the Fc fragment NO: 210 of IgG (CD16) SG211 SEQ ID 3689 ITGB2 Integrin, beta 2 (antigen CD18 (p95), NO: 211 antigen associated to the function of the lymphocytes 1; beta subunit of the microphage 1 (mac-1) antigen) SG212 SEQ ID 930 CD19 Antigen CD19 NO: 212 SG213 SEQ ID 931 MS4A1 Of 4 domains which are expanded by the NO: 213 membrane, subfamily A, member 1 SG214 SEQ ID 1380 CR2 Complement component receptor NO: 214 (3d/Epstein Barr's virus) 2 SG215 SEQ ID 933 CD22 Antigen CD22 NO: 215 SG216 SEQ ID 2208 FCER2 Low-affinity receptor II for the Fc fragment NO: 216 of IgE (CD23A) SG217 SEQ ID 934 CD24 Antigen CD24 (antigen of carcinoma of NO: 217 small lung cells of the grouping 4) SG218 SEQ ID 3559 IL2RA interleukin 2 receptor, alpha NO: 218 SG219 SEQ ID 1803 DPP4 Dipeptidyl peptidase IV (CD26, protein NO: 219 which forms complexes with adenosine deaminase 2) SG220 SEQ ID 3688 ITGB1 Integrin, beta 1 (fibronectin receptor, beta NO: 220 polypeptide, antigen CD29 includes MDF2, MSK12) SG221 SEQ ID 943 TNFRSF8 Tumour necrosing factor receptor NO: 221 superfamily, member 8 SG222 SEQ ID 945 CD33 Antigen CD33 (gp67) NO: 222 SG223 SEQ ID 947 CD34 Antigen CD34 NO: 223 SG224 SEQ ID 948 CD36 Antigen CD36 (collagen type I receptor, NO: 224 thrombospondin receptor) SG225 SEQ ID 952 CD38 Antigen CD38 (p45) NO: 225 SG226 SEQ ID 958 TNFRSF5 Tumour necrosing factor receptor NO: 226 superfamily, member 5 SG227 SEQ ID 6693 SPN Sarcospan (Gene associated to the Kras NO: 227 oncogene) SG228 SEQ ID 960 CD44 Antigen CD44 (homing function and Indian NO: 228 blood group function) SG229 SEQ ID 960 CD44v6 Antigen CD44 (homing function and Indian NO: 229 blood group function) SG230 SEQ ID 5788 PTPRCCD Protein thyrosine phosphatase, receptor NO: 230 type, C SG231 SEQ ID 961 CD47 Antigen CD47 (Antigen related to Rh, NO: 231 transducer of the signal associated to integrins) SG232 SEQ ID 3673 ITGA2 Integrin, alpha 2 (CD49B, alpha 2 subunit of NO: 232 receptor VLA-2) SG233 SEQ ID 3675 ITGA3 Integrin, alpha 3 (Antigen CD49C, alpha NO: 233 subunit 3 of receptor VLA-3) SG234 SEQ ID 3676 ITGA4 Integrin, alpha 4 (Antigen CD49D, alpha NO: 234 subunit 4 of receptor VLA-4) SG235 SEQ ID 3678 ITGA5 Integrin, alpha 5 (fibronectin receptor, alpha

NO: 235 polypeptide) SG236 SEQ ID 3385 ICAM3 Intercellular adhesion molecule 3 NO: 236 SG237 SEQ ID 1043 CDW52 Antigen CDW52 (antigen CAMPATH-1) NO: 237 SG238 SEQ ID 3383 ICAM1 Intercellular adhesion molecule 1 (CD54), NO: 238 human rhinovirus receptor SG239 SEQ ID 4684 NCAM1 Neural cell adhesion molecule 1 NO: 239 SG240 SEQ ID 965 CD58 Antigen CD58 (antigen associated to the NO: 240 function of the lymphocytes 3) SG241 SEQ ID 966 CD59 Antigen CD59 p18-20 (antigen identified by NO: 241 the monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344) SG242 SEQ ID 6402 SELL Selectin L (lymphocyte adhesion molecule NO: 242 1) SG243 SEQ ID 974 CD79B Antigen CD79B (associated to beta NO: 243 immunoglobulins) SG244 SEQ ID 975 CD81 Antigen CD81 (target of the antiproliferative NO: 244 antibody 1) SG245 SEQ ID 3732 KAI1 Kangai 1 (suppression of tumorigenicity 6, NO: 245 prostate; antigen CD82 (leukocytes R2 antigen, antigen detected by the monoclonal antibody IA4)) SG246 SEQ ID 9308 CD83 Antigen CD83 (activated B lymphocytes, NO: 246 immunoglobulins superfamily) SG247 SEQ ID 942 CD86 Antigen CD86 (ligand 2 of the antigen NO: 247 CD28, antigen B7-2) SG248 SEQ ID 355 TNFRSF6 Tumour necrosing factor receptor NO: 248 superfamily, member 6 SG249 SEQ ID 356 TNFSF6 Tumour necrosing factor receptor NO: 249 superfamily (ligand), member 6 SG250 SEQ ID 8140 SLC7A5 Solute-carrier family 7 (cationic amino acid NO: 250 carrier, y+ system), member 5 SG251 SEQ ID 6382 SDC1 Sindecan 1 NO: 251 SG252 SEQ ID 1019 CDK4 Cyclin-dependent kinase 4 NO: 252 SG253 SEQ ID 6774 STAT3 Signal transducer and transcription activator NO: 253 3 (response factor in acute phase) SG254 SEQ ID 2268 FGR Homologue to Gardner-Rasheed's feline NO: 254 viral sarcoma oncogene(v-fgr) SG255 SEQ ID 2353 FOS Homologue to the murine viral NO: 255 osteosarcoma oncogene V-fos FBJ SG256 SEQ ID 898 CCNE1 Cyclin E1 NO: 256 SG257 SEQ ID 978 CDA Cytidine deaminase NO: 257 SG258 SEQ ID 9935 MAFB Homologue to the fibrosarcoma NO: 258 oncogene (avian) musculoaponeurotic V- maf SG259 SEQ ID 4352 MPL Oncogene of myeloproliferative leukemia NO: 259 virus SG260 SEQ ID 4609 MYC Homologue to the avian myelocyomatosis NO: 260 viral oncogene V-myc SG261 SEQ ID 4602 MYB Homologue to the avian myelocyomatosis NO: 261 viral oncogene V-myb SG262 SEQ ID 1159 CKMT1 Creatine kinase, mitochondrial 1 (ubicuous) NO: 262 SG263 SEQ ID 1387 CREBBP CREB binding protein (Rubinstein-Taybi's NO: 263 syndrome) SG264 SEQ ID 1490 CTGF Connective tissue growth factor NO: 264 SG265 SEQ ID 2833 CXCR3 Chemokene receptor 3 (motive C--X--C) NO: 265 SG266 SEQ ID 7852 CXCR4 Chemokene receptor 4 (motive C--X--C) NO: 266 (fusin) SG267 SEQ ID 8900 CCNA1 Cyclin A1 NO: 267 SG268 SEQ ID 891 CCNB1 Cyclin B1 NO: 268 SG269 SEQ ID 894 CCND2 Cyclin D2 NO: 269 SG270 SEQ ID 1543 CYP1A1 Cytochrome P450, subfamily I (inducible by NO: 270 aromatic compounds), polypeptide 1 SG271 SEQ ID 1565 CYP2A6 Cytochrome P450, subfamily IID (of NO: 271 metabolization of debrisokine, spartin, etc.), polypeptide 6 SG272 SEQ ID 1603 DAD-1 Defender against cell death 1 NO: 272 SG273 SEQ ID 8794 TNFRSF10C Tumour necrosing factor receptor NO: 273 superfamily, member 10c, decoy without intracellular domain SG274 SEQ ID 7913 DEK Oncogene DEK (which binds to DNA) NO: 274 SG275 SEQ ID 1633 DCK Deoxycytidine kinase NO: 275 SG276 SEQ ID 1719 DHFR Dihydrofolate reductase NO: 276 SG277 SEQ ID 6929 TCF3 Transcription factor 3 (immunoglobulin NO: 277 enhancer binding factors E2A E12/E47) SG278 SEQ ID 1869 E2F1 Transcription factor E2F 1 NO: 278 SG279 SEQ ID 6929 TCF3 Transcription factor 3 (immunoglobulin NO: 279 enhancer binding factors E2A E12/E47) SG280 SEQ ID 56899 EB-1 Protein associated to E2a-Pbx1 NO: 280 SG281 SEQ ID 1236 CCR7 Chemokene receptor 7 (motive C-C) NO: 281 SG282 SEQ ID 1880 EBI2 Gene induced by Epstein-Barr's 2 disease NO: 282 (receptor coupled to G proteins specific for lymphocytes) SG283 SEQ ID 4582 MUC-1 Mucin 1, transmembrane NO: 283 SG284 SEQ ID 2042 EphA3 EPHA3 NO: 284 SG285 SEQ ID 2057 EPOR Erythropoietin receptor NO: 285 SG286 SEQ ID 2067 ERCC1 Of repair of excision which NO: 286 intercomplements the deficiency in the repair of rodents, complementation group 1 (includes the antisense overlapping sequence) SG287 SEQ ID 2068 ERCC2 Of repair of excision which NO: 287 intercomplements the deficiency in the repair of rodents, complementation group 2 (xerodermia pigmentoso 2) SG288 SEQ ID 2071 ERCC3 Of repair of excision which NO: 288 intercomplements the deficiency in the repair of rodents, complementation group 3 (complements group B of xerodermia pigmentoso) SG289 SEQ ID 2073 ERCC5 Of repair of excision which NO: 289 intercomplements the deficiency in the repair of rodents, complementation group 5 (xerodermia pigmentoso, complementation group G (Cockayne's syndrome)) SG290 SEQ ID 2074 ERCC6 Of repair of excision which NO: 290 intercomplements the deficiency in the repair of rodents, complementation group 6 SG291 SEQ ID 50624 CUZD1 With CUB domains and similar to the zone NO: 291 pellucida 1 SG292 SEQ ID 2120 ETV6 Gene variant of ets 6 (TEL oncogene) NO: 292 SG293 SEQ ID 1977 EIF4E Initiation factor of eukaryotic translation 4E NO: 293 SG294 SEQ ID 1984 EIF5A Initiation factor of eukaryotic translation 5A NO: 294 SG295 SEQ ID 2146 EZH2 Zeste homologue enhancer (Drosophila) 2 NO: 295 SG296 SEQ ID 8772 FADD Associated to Fas (TNFRSF6) via NO: 296 apoptopic domain SG297 SEQ ID 5747 PTK2 Thyrosine kinase 2 protein NO: 297 SG298 SEQ ID 2195 FAT Homologue to the FAT tumour suppressor NO: 298 (Drosophila) SG299 SEQ ID 2260 FGFR1 Fibroblast growth factor receptor 1 NO: 299 (thyrosine kinase related to fms 2, Pfeiffer's syndrome) SG300 SEQ ID 2261 FGFR3 Fibroblast growth factor receptor 3 NO: 300 (achondroplasia, thanatophoric dwarfism) SG301 SEQ ID 2272 FHIT Fragile histidine triad gene NO: 301 SG302 SEQ ID 2322 FLT3 Thyrosine kinase related to Fms 3 NO: 302 SG303 SEQ ID 2892 GRIA3 Glutamate receptor, ionotrophic, AMPA 3 NO: 303 SG304 SEQ ID 2521 FUS Fusion, derived from the malignant NO: 304 liposarcoma t(12;16) SG305 SEQ ID 1977 EIF4E Initiation factor of eukaryotic translation 4E NO: 305 SG306 SEQ ID 6482 SIAT4A Sialyltransferase 4A (beta-galactosidase NO: 306 alpha-2.3-Sialyltransferase) SG307 SEQ ID 1440 CSF3 Colony stimulating factor 3 (granulocyte) NO: 307 SG308 SEQ ID 1437 CSF2 Colony stimulating factor 2 (granulocyte- NO: 308 microphage) SG309 SEQ ID 2908 NR3C1 Subfamily of nuclear receptors 3, group C, NO: 309 member 1 SG310 SEQ ID 2952 GSTT1 Glutathion S-transferase theta 1 NO: 310 SG311 SEQ ID 3001 GZMA Granzime A (granzime 1, serine stearase NO: 311 associated to cytotoxic T lymphocytes 3) SG312 SEQ ID 3301 DNAJA1 Homologue to DnaJ (Hsp40), subfamily A, NO: 312 member 1 SG313 SEQ ID 3131 HLF Hepatic leukemia factor NO: 313 SG314 SEQ ID 684 BST2 Antigen of bone marrow stroma cells 2 NO: 314 SG315 SEQ ID 3205 HOXA9 Homeotic box A9 NO: 315 SG316 SEQ ID 3195 TLX1 T lymphocyte leukemia, homeotic box 1 NO: 316 SG317 SEQ ID 29128 UHRF1 similar to ubiquitine, which contains PHD NO: 317 domains and RING fingers, 1 SG318 SEQ ID 8870 IER3 Immediate early response 3 NO: 318 SG319 SEQ ID 3553 IL1B Interleukin 1, beta NO: 319 SG320 SEQ ID 3558 IL2 Interleukin 2 NO: 320 SG321 SEQ ID 3562 IL3 Interleukin 3 (multiple colony stimulating NO: 321 factor) SG322 SEQ ID 3569 IL6 Interleukin 6 (interferon, beta 2) NO: 322 SG323 SEQ ID 3570 IL6R Interleukin receptor 6 NO: 323 SG324 SEQ ID 3586 IL10 Interleukin 10 NO: 324 SG325 SEQ ID 3600 IL15 Interleukin 15 NO: 325 SG326 SEQ ID 3662 IRF4 Interferon regulating factor 4 NO: 326 SG327 SEQ ID 3716 JAK1 Janus 2 kinase (a thyrosine kinase protein) NO: 327 SG328 SEQ ID 3717 JAK2 Janus 1 kinase (a thyrosine kinase protein) NO: 328 SG329 SEQ ID 4288 MKI67 Antigen identified by monoclonal antibody NO: 329 Ki-67 SG330 SEQ ID 7520 XRCC5 Of repair of X rays which complements the NO: 330 defective repair in Chinese hamster cells 5 (reconnection of breakages in the double helix; autoantigen Ku, 80 kDa) SG331 SEQ ID 3902 LAG3 Lymphocyte activation gene 3 NO: 331 SG332 SEQ ID 3932 LCK Lymphocyte specific protein thyrosine NO: 332 kinase SG333 SEQ ID 3936 LCP1 Cytosolic protein of lymphocytes 1 (L- NO: 333 plastin) SG334 SEQ ID 3953 LEPR Leptin receptor NO: 334 SG335 SEQ ID 4005 LMO2 With LIM domains only 2 (similar to NO: 335 rombotin 1) SG336 SEQ ID 3976 LIF Leukemia inhibiting factor (cholinergic NO: 336 differentiation factor) SG337 SEQ ID 9961 LRP Main leap protein NO: 337 SG338 SEQ ID 4046 LSP1 Lymphocyte-specific protein 1 NO: 338 SG339 SEQ ID 4066 LYL1 Sequence derived from lymphoblastic NO: 339 leukemia 1 SG340 SEQ ID 4790 NFKB1 Nuclear factor of the enhancer of the gene NO: 340 of the light kappa polypeptide in B-1 lymphocytes(p105) SG341 SEQ ID 4118 MAL mal, T lymphocyte differentiation protein NO: 341 SG342 SEQ ID 4100 MAGEA1 Melanoma antigen, family A, 1 (directs the NO: 342 expression of antigen MZ2-E) SG343 SEQ ID 5602 MAPK10 Protein kinase activated by mitogens 10 NO: 343 SG344 SEQ ID 2023 MBP1 Enolase 1, (alpha) NO: 344 SG345 SEQ ID 4170 MCL1 Leukemia sequence of myeloid cells 1 NO: 345 (related to BCL2) SG346 SEQ ID 4193 MDM2 Human homologue of the double mouse NO: 346 diminuta 2; p53-binding protein SG347 SEQ ID 5243 ABCB1 ATP binding module, subfamily B NO: 347 (MDR/TAP), member 1 SG348 SEQ ID 5244 ABCB4 ATP binding module, subfamily B NO: 348 (MDR/TAP), member 4 SG349 SEQ ID 4221 MEN1 Multiple endocrine neoplasia I

NO: 349 SG350 SEQ ID 4283 CXCL9 Chemokene ligand 9 (motive C--X--C) NO: 350 SG351 SEQ ID 4291 MLF1 Myeloid leukemia factor 1 NO: 351 SG352 SEQ ID 4297 MLL Myeloid/lymphoid leukemia or of mixed line NO: 352 (homologue to trithorax (Drosophila)) SG353 SEQ ID 4318 MMP9 Metalloproteinase of matrix 9 (gelatinase B, NO: 353 92 kD gelatinase, 92 kD collagenase type IV) SG354 SEQ ID 4707 NDUFB NADH dehydrogenase (ubiquinone) 1 beta NO: 354 subcomplex, 1 (7 kD, MNLL) SG355 SEQ ID 4353 MPO Myeloperoxidase NO: 355 SG356 SEQ ID 8714 ABCC3 ATP binding module, subfamily C NO: 356 (CFTR/MRP), member 3 SG357 SEQ ID 10057 ABCC5 ATP binding module, subfamily C NO: 357 (CFTR/MRP), member 5 SG358 SEQ ID 4515 MTCP1 Proliferation of mature T-lymphocytes 1 NO: 358 SG359 SEQ ID 4515 MTCP1 Proliferation of mature T-lymphocytes 1 NO: 359 SG360 SEQ ID 4654 MYOD1 Myogenic factor 3 NO: 360 SG361 SEQ ID 4599 MX1 Resistance to Myxovirus (flu) 1, homologue NO: 361 to the murine protein (protein inducible by interferon p78) SG362 SEQ ID 4814 NINJ1 Ninjurin 1 NO: 362 SG363 SEQ ID 4869 NPM1 Nucleophosmin (nucleolar phosphoprotein NO: 363 B23, numatrin) SG364 SEQ ID 9235 IL32 Interleukin 32 NO: 364 SG365 SEQ ID 4926 NUMA1 Nuclear protein of the myotic apparatus 1 NO: 365 SG366 SEQ ID 5452 POU2F2 transcription factor with POU domain, of NO: 366 class 2, 2 SG367 SEQ ID 5452 POU2F2 transcription factor with POU domain, of NO: 367 class 2, 2 SG368 SEQ ID 4968 OGGI 8-oxoguanine-DNA-glycosilase NO: 368 SG369 SEQ ID 1030 CDKN2B Cyclin-dependent kinase inhibitor 2B (p15, NO: 369 inhibits CDK4) SG370 SEQ ID 1029 CDKN2A Cyclin-dependent kinase inhibitor 2A NO: 370 (melanoma, p16, inhibits CDK4) SG371 SEQ ID 1031 CDKN2C Cyclin-dependent kinase inhibitor 2C (p18, NO: 371 inhibits CDK4) SG372 SEQ ID 1026 CDKN1A Cyclin-dependent kinase inhibitor 1A (p21, NO: 372 Cip1) SG373 SEQ ID 1027 CDKN1B Cyclin-dependent kinase inhibitor 1B (p27, NO: 373 Kip1) SG374 SEQ ID 8851 CDK5R1 Cyclin-dependent kinase 5, regulator NO: 374 subunit 1 (p35) SG375 SEQ ID 10210 TOPORS Of binding to topoisomerase I, rich inc NO: 375 arginine/serine SG376 SEQ ID 991 P55CDC CDC20 (cell division cycle 20, S. cerevisiae, NO: 376 homologue) SG377 SEQ ID 1028 CDKN1C Cyclin-dependent kinase inhibitor 1C (p57, NO: 377 Kip2) SG378 SEQ ID 7161 TP73 Tumour protein p73 NO: 378 SG379 SEQ ID 5079 PAX5 Paired box gene 5 (specific activating NO: 379 protein of the B lymphocytes line) SG380 SEQ ID 5087 PBX1 Transcription factor of B 1 prelymphocytes NO: 380 leukemia SG381 SEQ ID 5090 PBX3 Transcription factor of B prelymphocytes NO: 381 leukemia B 3 SG382 SEQ ID 5089 ENPP1 Ectonucleotide NO: 382 pyrophosphatase/phosphodiesterase 1 SG383 SEQ ID 5167 PCA1 Ectonucleotide NO: 383 pyrophosphatase/phosphodiesterase 1 SG384 SEQ ID 5111 PCNA Nuclear antigen of proliferating cells NO: 384 SG385 SEQ ID 5159 PDGFRB Platelet-derived growth factor receptor, beta NO: 385 polypeptide SG386 SEQ ID 5588 PRKCQ kinase C protein, theta NO: 386 SG387 SEQ ID 5347 PLK1 Plasminogen activator, urokinase NO: 387 SG388 SEQ ID 5371 PML Promielocytic leukemia NO: 388 SG389 SEQ ID 23532 PRAME Antigen expressed preferentially in NO: 389 melanoma SG390 SEQ ID 5584 PRKCI protein kinase C, iota NO: 390 SG391 SEQ ID 5728 PTEN Phosphatase and homologue to tensin NO: 391 (mutated in multiple advanced cancers 1) SG392 SEQ ID 5742 PTGS1 prostaglandin-endoperoxide synthase 1 NO: 392 (prostaglandin G/H synthase and cyclooxigenase) SG393 SEQ ID 5744 PTHLH Hormone similar to the parathyroidal NO: 393 hormone SG394 SEQ ID 6688 SPI1 Oncogene of integration of provirus of focus NO: 394 forming virus in the spleen (SFFV) spi1 SG395 SEQ ID 2185 PTK2B Thyrosine kinase 2 beta protein NO: 395 SG396 SEQ ID 5889 RAD51 Homologue to RAD51 (S. cerevisiae) NO: 396 (homologue to RecA of E. coli) SG397 SEQ ID 5896 RAG1 Recombination activator gene 1 NO: 397 SG398 SEQ ID 5914 RARA Retinoic acid receptor, alpha NO: 398 SG399 SEQ ID 3845 KRAS2 Homologue to the viral oncogene of Kirsten NO: 399 2 V-Ki-ras2 rat sarcoma SG400 SEQ ID 5925 RB1 Retinoblastoma 1 (including osteosarcoma) NO: 400 SG401 SEQ ID 7422 VEGF Vascular endothelial growth factor NO: 401 SG402 SEQ ID 7791 ZYX Zyxin NO: 402 SG403 SEQ ID 940 CD28 Antigen CD28 (Tp44) NO: 403 SG404 SEQ ID 940 CD28 Antigen CD28 (Tp44) NO: 404 SG405 SEQ ID 1656 RBBP4 retinoblastoma 4 binding protein NO: 405 SG406 SEQ ID 1656 DDX6 Polypeptide with DEAD/H box (Asp-Glu- NO: 406 Ala-Asp/His) 6 (RNA helicase, 54 kD) SG407 SEQ ID 5928 APEX APEX nuclease (multifunctional DNA repair NO: 407 enzyme DNA) SG408 SEQ ID 5977 DPF2 D4, family 2 with zinc fingers and double NO: 408 PHD SG409 SEQ ID 5996 RGS1 G protein signalling regulator G 1 NO: 409 SG410 SEQ ID 3161 HMMR Motility receptor mediated by hyaluronane NO: 410 (RHAMM) SG411 SEQ ID 6777 STAT5B signal transducer and transcription activator NO: 411 5B SG412 SEQ ID 332 BIRC5 Which contains IAP repetitions of NO: 412 baculovirus 5 (survivin) SG413 SEQ ID 6886 TAL1 Acute lymphocytic leukemia of T NO: 413 lymphocytes 1 SG414 SEQ ID 10482 NXF1 RNA exportation nuclear factor of RNA 1 NO: 414 SG415 SEQ ID 8115 TCL1A Leukemia/lymphoma of T 1A lymphocytes NO: 415 SG416 SEQ ID 6955 TRA@ T locus alpha lymphocyte receptor NO: 416 SG417 SEQ ID TCR beta mRNA of the beta chain of the T NO: 417 lymphocyte receptor (TCRB) of Homo sapiens SG418 SEQ ID 1791 DNTT Deoxynucleotidyl transferase, terminal NO: 418 SG419 SEQ ID 7015 TERT Inverse telomerase transcriptase NO: 419 SG420 SEQ ID 2066 ERBB4 Similar to the homologue to the viral NO: 420 oncogene of avian erythroblastic leukemia V-erb-a 4 SG421 SEQ ID 2064 ERBB2 Homologue to the to the viral oncogene of NO: 421 avian erythroblastic leukemia V-erb-b2 2 (homologue to the oncogene derived from neuro/glioblastoma) SG422 SEQ ID 1956 EGFR Epidermal growth factor receptor NO: 422 (homologue to the viral oncogene of avian erythroblastic leukemia (v-erb-b)) SG423 SEQ ID 7066 THPO Thrombopoietin (oncogene ligand of the NO: 423 myeloproliferative leukemia virus, growth factor and development of megakaryocytes) SG424 SEQ ID 7074 TIAM1 Invasion and metastasis of lymphoma of T NO: 424 lymphocytes 1 SG425 SEQ ID 7083 TK1 Thymidine kinase 1, soluble NO: 425 SG426 SEQ ID 7132 TNFRSF1A Tumour necrosing factor receptor NO: 426 superfamily, member 1A SG427 SEQ ID 7153 TOP2A Topoisomerase (DNA) II alpha (170 kD) NO: 427 SG428 SEQ ID 1052 CEBPD binding protein to CCAAT/enhancer NO: 428 (C/EBP), delta SG428 SEQ ID 9214 FAIM3 Apoptosis inhibitor molecule mediated by NO: 428 Fas 3 SG429 SEQ ID 5358 PLS3 Plastin 3 (isoform T) NO: 429 SG430 SEQ ID 8717 TRADD associated to TNFRSF1A via the cell death NO: 430 domain SG431 SEQ ID 8743 TNFSF10 Tumour necrosing factor superfamily NO: 431 (ligand) member 10 SG432 SEQ ID 10131 TRAP 1 Thermal shock protein 75 NO: 432 SG433 SEQ ID 7057 THBS1 Thrombospondin 1 NO: 433 SG434 SEQ ID 7341 SUMO1 Homologue to the supressor of mif two 3 NO: 434 SMT3 1 (yeast) SG435 SEQ ID 7405 UVRAG Gene associated to UV radiation resistance NO: 435 SG436 SEQ ID 7441 VPREB1 Gene of B 1 prelymphocytes NO: 436 SG437 SEQ ID 51384 WNT16 family of MMTV integration site, Wingless- NO: 437 type, member 16 SG438 SEQ ID 7490 WT1 Wilms tumour 1 NO: 438 SG439 SEQ ID 7517 XRCC3 Of repair of X rays which complement the NO: 439 defective repair in Chinese hamster cells 3 SG440 SEQ ID 896 CCND3 Cyclin D3 NO: 440 SG441 SEQ ID 1017 CDK2 Cyclin-dependent kinase 2 NO: 441 SG442 SEQ ID p14ARF Gene p14ARF from Homo sapiens, NO: 442 promoter region, complete sequence SG443 SEQ ID 3070 HELLS Helicase, specific for lymphoid cells NO: 443 SG444 SEQ ID 2624 GATA2 GATA 1-binding protein 2 NO: 444 SG445 SEQ ID 2623 GATA1 GATA 1-binding protein (globin transcription NO: 445 factor 1) SG446 SEQ ID 8028 MLLT10 Myeloid/lymphoid leukemia or of mixed line NO: 446 (homologue to trithorax (Drosophila)); translocated to 10 SG447 SEQ ID 8301 PICALM Clathrin assembly protein which binds to NO: 447 phosphatidylinositol SG448 SEQ ID 3815 KIT Homologue to the viral oncogene of Hardy- NO: 448 Zuckerman's feline sarcoma 4 V-kit SG449 SEQ ID 3563 IL3RA Interleukin 3 receptor, alpha (low affinity) NO: 449 SG450 SEQ ID 1050 CEBPA binding protein to CCAAT/enhancer NO: 450 (C/EBP), alpha SG451 SEQ ID 3655 ITGA6 Integrin, alpha 6 NO: 451 SG452 SEQ ID 84955 CML66 Tumour antigen of chronic myelogenous NO: 452 leukemia 66 SG453 SEQ ID 7187 TRAF3 Factor associated to the TNF receptor 3 NO: 453 SG454 SEQ ID 1612 DAPK1 Kinase protein associated to cell death 1 NO: 454 SG455 SEQ ID 8788 MAP3K12 Homologue similar to Delta (Drosophila) NO: 455 SG456 SEQ ID 5591 PRKDC Kinase protein, activated by DNA, catalytic NO: 456 polypeptide SG457 SEQ ID 1789 DNMT3B (cytosine-5-)-methyltransferase 3 beta of NO: 457 DNA SG458 SEQ ID 2950 GSTP1 Glutathion S-transferase pi NO: 458 SG459 SEQ ID 3122 HLA-DRA Complex greater than histocompatibility, NO: 459 class II, DR alpha SG460 SEQ ID 3206 HOXA10 Homeotic box A10 NO: 460 SG461 SEQ ID 3394 IRF8 Binding protein to the agreed sequence of NO: 461 interferon 1 SG462 SEQ ID 3398 ID2 DNA binding inhibitor 2, negative dominant NO: 462 helix-loops-helix protein SG463 SEQ ID 60 ACTB Actin, beta NO: 463 SG464 SEQ ID 60 ACTB Actin, beta NO: 464 SG465 SEQ ID 2868 GRK4 Kinase of receptor coupled to a protein G 4 NO: 465 SG466 SEQ ID 2597 GAPD Glyceraldehyde-3-phosphate NO: 466 dehydrogenase SG467 SEQ ID 2597 GAPD Glyceraldehyde-3-phosphate NO: 467 dehydrogenase SG468 SEQ ID 6772 STAT1 Signal transducer and transcription activator NO: 468 1, 91 kDa SG469 SEQ ID 18S rRNA Human rRNA gene 18S

NO: 469 SG470 SEQ ID 7037 TFRC Transferrin receptor (p90, CD71) NO: 470 SG471 SEQ ID 28S rRNA Human ribosomal RNA gene 28S NO: 471 SG472 SEQ ID 6168 RPL37A Ribosomal protein L37a NO: 472 SG473 SEQ ID 6171 RPL41 Ribosomal protein L41 NO: 473 SG474 SEQ ID 3191 HNRPL Heterogeneous nucler ribonucleoprotein L NO: 474 SG475 SEQ ID 3608 ILF2 Binding factor to the interleukin-2 enhancer, NO: 475 45 kD SG476 SEQ ID 8407 TAGLN2 Transgelin 2 NO: 476 SG477 SEQ ID 824 CAPN2 Calpain 2, (m/II) major subunit NO: 477 SG478 SEQ ID 5686 PSMA5 Subunit of proteasome (prosome, NO: 478 macropain), type alpha, 5 SG479 SEQ ID 27254 PMM1 Phosphomannomutase 1 NO: 479 SG480 SEQ ID 8079 MLF2 Myeloid leukemia factor 2 NO: 480 SG481 SEQ ID 5501 PPP1CC Phosphatase protein 1, catalytic subunit, NO: 481 gamma isoform SG482 SEQ ID 22794 CASC3 Candidate for susceptibility to cancer 3 NO: 482 SG483 SEQ ID 23164 KIAA0864 Protein KIAA0864 NO: 483 SG484 SEQ ID 7296 TXNRD1 Thioredoxine reductase 1 NO: 484 SG485 SEQ ID 5713 PSMD7 Subunit of proteasome (prosome, NO: 485 macropain) 26S, no-ATPase, 7 (homologue to Mov34) SG486 SEQ ID 8892 EIF2B2 initiation factor of eukaryotic translation 2B, NO: 486 subunit 2 (beta, 39 kD) SG487 SEQ ID 3105 HLA-A Complex greater than histocompatibility, NO: 487 class I, A SG488 SEQ ID 4176 MCM7 Minichromosome maintenance deficient (S. cerevisiae) 7 NO: 488 SG489 SEQ ID 8718 TNFRSF25 Tumour necrosing factor receptor NO: 489 superfamily, member 25 SG490 SEQ ID 3958 LGALS3 Lectin, which binds to galactosides, soluble, NO: 490 3 (galectin 3) SG491 SEQ ID 311 HLA-DPA1 Complex greater than histocompatibility, NO: 491 class II, DP alpha 1 SG492 SEQ ID 5328 PLAU Plasminogen activator, urokinase NO: 492 SG493 SEQ ID 1281 COL3A1 Collagen, type III, alpha 1 (Ehlers-Danlos NO: 493 type IV syndrome, dominant autosomal) SG494 SEQ ID 287 ANK2 Ankyrin 2, neuronal NO: 494 SG495 SEQ ID 327657 SERPINA9 serine (or cysteine) proteinase inhibitor, NO: 495 clade A (alpha-1 antiproteinase, antitrypsin), member 9 SG496 SEQ ID 10360 NPM3 Nucleophosmin/nucleoplasmin 3 NO: 496 SG497 SEQ ID 1235 CCR6 Receptor 6 of chemokenes (motive C-C) NO: 497 SG498 SEQ ID 3055 HCK Hematopoietic cell kinase NO: 498 SG499 SEQ ID 26354 GNL3 similar to guanine 3 nucleotide binding NO: 499 protein (nucleolar) SG500 SEQ ID 2885 GRB2 Protein bound to growth factor receptor 2 NO: 500 SG501 SEQ ID 597 BCL2A1 protein related to BCL2 A1 NO: 501 SG502 SEQ ID 1997 ELF1 Factor similar to E74 1 (transcription factor NO: 502 with ets domain) SG503 SEQ ID 1508 CTSB Catepsin B NO: 503 SG504 SEQ ID 257144 GCET2 transcript expressed in the budding centre 2 NO: 504 SG505 SEQ ID 2335 FN1 Fibronectin 1 NO: 505 SG506 SEQ ID 5133 PDCD1 Programme cell death 1 NO: 506 SG507 SEQ ID 3125 HLA-DRB3 Complex greater than histocompatibility, NO: 507 class II, DR beta 3 SG508 SEQ ID 3117 HLA-DQA1 Complex greater than histocompatibility, NO: 508 class II, DQ alpha 1 SG509 SEQ ID 257144 GCET2 transcript expressed in the budding centre NO: 509 germinal 2 SG510 SEQ ID 327657 SERPINA9 serine (or cysteine) proteinase inhibitor, NO: 510 clade A (alpha-1 antiproteinase, antitrypsin), member 9 SG511 SEQ ID 1033 CDKN3 Cyclin dependent kinases 3 (phosphatase NO: 511 of dual specificity associated CDK2) SG512 SEQ ID 1997 ELF1 Factor similar to E74 1 (transcription factor NO: 512 with ets domain) SG513 SEQ ID 1509 CATSD Catepsin D (liposomal aspartylprotease) NO: 513 SG514 SEQ ID 3315 HSPB1 Thermal shock protein of 27 kD 1 NO: 514 SG515 SEQ ID 87 ACTN1 Actinin, alpha 1 NO: 515 SG516 SEQ ID 654 BMP6 Morphogenetic bone protein 6 NO: 516 SG517 SEQ ID 9780 FAM38A family with similarity of sequence 38, member A NO: 517 SG518 SEQ ID 962 CD48 Antigen CD48 (membrane protein of B NO: 518 lymphocytes) SG519 SEQ ID 3566 IL4R Interleukin 4 receptor NO: 519 SG520 SEQ ID 1821 DRP2 Dystrophin related protein 2 NO: 520 SG521 SEQ ID 3726 JUNB Jun B Proto-oncogene NO: 521 SG522 SEQ ID 6279 S100A8 Calcium-binding protein S100 A8 NO: 522 (calgranuline A) SG523 SEQ ID 10320 ZNFN1A1 Protein with zinc fingers, subfamily 1A, 1 NO: 523 (lkaros) SG524 SEQ ID 10461 MERTK Thyrosine kinase of the C-mer proto- NO: 524 oncogene SG525 SEQ ID 51621 KLF13 Factor similar to that of Kruppel 13 NO: 525 SG526 SEQ ID 865 CBFB Nucleus-binding factor, beta subunit NO: 526 SG527 SEQ ID 1051 CEBPB binding protein to CCAAT/enhancer NO: 527 (C/EBP), beta SG529 SEQ ID 7024 TFCP2 Transcription factor CP2 NO: 529 SG530 SEQ ID 1385 CREB1 CAMP response element binding protein NO: 530 SG531 SEQ ID 4782 NFIC I/C nuclear factor (CCAAT binding factor NO: 531 transcription factor) SG532 SEQ ID 2553 GABPB2 Transcription factor of the protein which NO: 532 binds to GA, beta 2 subunit (47 kD) SG533 SEQ ID 1958 EGR1 Early growth response 1 NO: 533 SG534 SEQ ID 10661 KLF1 Factor similar to that of Kruppel 1 NO: 534 (erythroid) SG535 SEQ ID 1997 ELF1 Factor similar to E74 1 (transcription factor NO: 535 with ets domain) SG536 SEQ ID 2113 ETS1 homologue to the E26 oncogene of NO: 536 erythroblastosis virus v-ets 1 (avian) SG537 SEQ ID 2114 ETS2 homologue to the E26 oncogene of NO: 537 erythroblastosis virus v-ets 2 (avian) SG538 SEQ ID 2313 FLI1 Integration of Friend 1 leukemia virus NO: 538 SG539 SEQ ID 2625 GATA3 GATA 3 binding protein NO: 539 SG540 SEQ ID 862 CBFA2T1 Nucleus binding factor, runt domain, alpha NO: 540 2 subunit; translocated to 1; related to cyclin D SG541 SEQ ID 3091 HIF1A Factor inducible by hypoxia 1, alpha subunit NO: 541 (basic transcription factor of helix-loops- helix) SG542 SEQ ID 6927 TCF1 Transcription factor 1, hepatic; LF-B1, NO: 542 hepatic nuclear factor (HNF1), proximal factor of albumin SG543 SEQ ID 3234 HOXD8 Homeotic box D8 NO: 543 SG544 SEQ ID 3235 HOXD9 Homeotic box D9 NO: 544 SG545 SEQ ID 9935 MAFB Family of the oncogene of NO: 545 musculoaponeurotic fibrosarcoma (avian) V-maf SG546 SEQ ID 7975 MAFK Family of the oncogene of NO: 546 musculoaponeurotic fibrosarcoma (avian) V-maf, protein K SG547 SEQ ID 8721 EDF1 factor related to edothelialdifferentiation 1 NO: 547 SG548 SEQ ID 2000 ELF4 Factor similar to E74 4 (transcription factor NO: 548 with ets domain) SG549 SEQ ID 7593 ZNF42 Protein with zinc fingers 142 (clone pHZ-49) NO: 549 SG550 SEQ ID 4763 NF1 neurofibromin 1 NO: 550 SG551 SEQ ID 4772 NFATC1 Nuclear factor of activated T-lymphocytes, NO: 551 cytoplasmic, calcineurin 1-dependent SG552 SEQ ID 5080 PAX6 Paired box gene 6 (aniridia, keratitis) NO: 552 SG553 SEQ ID 7849 PAX8 Paired box gene 8 NO: 553 SG554 SEQ ID 57026 PLP Pyridoxal (pyridoxine, vitamin B6) NO: 554 phosphatase SG555 SEQ ID 2274 PLZF With four LIM domains and average 2 NO: 555 SG556 SEQ ID 5950 RBP4 Retinol 4-binding protein, plasma NO: 556 SG557 SEQ ID 6095 RORA Orphan receptor related to RAR A NO: 557 SG558 SEQ ID 6667 SP1 Transcription factor Sp1 NO: 558 SG559 SEQ ID 6772 STAT1 Signal transducer and transcription activator NO: 559 1, 91 kDa SG560 SEQ ID 6908 TBP TATA box-binding protein NO: 560 SG561 SEQ ID 6932 TCF7 Transcription factor 7 (T lymphocyte NO: 561 specific, box HMG) SG562 SEQ ID 51513 ETV7 Gene variant of ets 7 (oncogene TEL2) NO: 562 SG563 SEQ ID 7535 ZAP70 Zeta chain associated kinase protein (TCR) NO: 563 (70 kD)

[0145] From among these genes, four of them (ACTB, GAPD, 18S rRNA and 28S rRNA), do not have a special relation with neoplasias and were initially included in the microarray because, for a long time, it was believed that their expression remained constant and they were used when normalizing the microarray data: they are the type of genes alluded to when we speak of "constitutive" genes at other points in the specification. At present, it is not thought that there is a gene whose expression remains constant in any circumstance, for which reason, in the present study, the genes ACTB, GAPD, 18S rRNA and 28S rRNA have received the same treatment as the other genes of the microarray, except for the fact that the first two of them have been used as integrity controls, as described further on.

[0146] In Table 1 it can be observed that there are genes which are represented by more than one oligonucleotide. This is the case because the existence of two or more probes per gene can be used to measure the integrity of the synthesized cRNA. The genes for which more than one oligonucleotide have been designed to act as probe, each one of which hybridizes with a different sequence, are indicated below in Table 2.

TABLE-US-00002 TABLE 2 Genes represented by more than one oligonucleotide as probe Usual abbreviation of the gene Probe1 Probe2 Probe3 ABL1 SG10 SG180 BCR SG169 SG170 CBFB SG189 SG526 CD28 SG403 SG404 EIF4E SG293 SG305 ELF1 SG512 SG535 SG502 ETS2 SG95 SG537 GCET2 SG504 SG509 MAFB SG258 SG545 MTCP1 SG358 SG359 POU2F2 SG366 SG367 RGS1 SG56 SG409 S100A2 SG35 SG71 SNRPB SG142 SG143 STAT1 SG77 SG559 SG468 TIA-2 SG7 SG73 TAGLN2 SG24 SG476 TCF3 SG277 SG279 XRCC5 SG32 SG330 ZYX SG97 SG402 CD44 SG228 SG229 ACTB SG463 SG464 GAPD SG464 SG467

Establishment of Control Probes

[0147] To decrease the variability, a large number of controls were included in each microarray. These controls suppose an objective measurement on the process quality, and therefore, of the quality of the data obtained. They are of several types and origins:

[0148] a) Probes Used as Integrity Controls

[0149] These probes were 2 pairs of oligonucleotides complementary to ends 5' and 3' of the .beta.-actin genes (probes code SG463 and SG464) and glyceraldehyde-3-phosphate dehydrogenase (probes code SG466 and SG467). The ratio between the intensities of the probe located at end 3' and 5' makes it possible to check the quality of the starting RNA and the functioning of the labelling reaction. The details on these oligonucleotides appear in Table 3.

TABLE-US-00003 TABLE 3 Oligonucleotides used as integrity controls Oligo- Gene GenID nucleotide SEQ ID NO: Source gene Abbreviation No. SG463 SEQ ID .beta.-actin ACTB 60 NO: 463 SG464 SEQ ID .beta.-actin ACTB 60 NO: 464 SG466 SEQ ID Glyceraldehyde-3- GAPD 2597 phosphate NO: 466 dehydrogenase SG467 SEQ ID Glyceraldehyde-3- GAPD 2597 phosphate NO: 467 dehydrogenase

b) Probes Used as Negative Controls

[0150] These probes are largely formed by a group of oligonucleotides of 50 nucleotides (50-mer) which are not complementary to any known human sequence. For them, the BLAST tool was applied to these probes and it was observed that they did not hybridize with any human sequence. They are identified with codes SC1 (SEQ ID NO:564), SC2 (SEQ ID NO:565), SC3 (SEQ ID NO:566), SC4 (SEQ ID NO:567), SC5 (SEQ ID NO:568), SC6 (SEQ ID NO:569) and SC7 (SEQ ID NO:570) and oligonucleotides SCN1 (SEQ ID NO:571), SCN5 (SEQ ID NO:575), SCN7 (SEQ ID NO:577) and SCN10 (SEQ ID NO:580) are also used as negative controls. They are used to determine the optimum conditions of hybridization, washing and developing of the chips or microarrays. The appearance of a signal associated to them indicates the existence of non-specific hybridization.

[0151] c) Exogenous Probes Used as Internal Positive Controls: "Spiked Controls"

[0152] "Spiked controls" are synthetic oligonucleotides whose sequence coincides with a fragment of a transcript of a non-human gene or of any other sequence of nucleotides of low homology with transcripts of human genes which is polyadenylated at 3', which is used as positive control, in the determination of the process quality, in the normalization of data and for the establishment of the linear range of the process (Benes V et al., 2003). To do this, the transcripts or corresponding polyadenylated sequences are added to the total starting RNA before starting the labelling process, and therefore, they suffer the same reactions (labelling, hybridization and developing) as the total

[0153] RNA of the samples.

[0154] 7 "Spiked controls" are used. To ensure low homology with human genes 5 transcripts of Bacillus subtilis genes (dap, thr, trp, phe and lys) and 2 transcripts of genes of the Sharkav virus are used, frequently referred to as "Plum poxvirus" (Sppv), which is a plant virus. The details on these oligonucleotides are shown below in Table 4. The ATCC (American Type Culture Collection) numbers which appear after the name of the source genes refer to the identification number in the ATCC of E. coli strains containing recombinant plasmids which contain the sequence of the genes from which the transcripts added to the RNA are obtained and which were also used for the design of the sequences of the corresponding oligonucleotides bound to the microarray.

TABLE-US-00004 TABLE 4 Oligonucleotides used as "Spiked Controls" Concentration Transcript (pM) in the Oligo- Gene Bank size "spiked controls" nucleotides SEQ ID NO: Source gene code (nt) solution SSPC1 SEQ ID Dap L38424 1820 2000 NO: 584 (ATCC no. 87486) SSPC2 SEQ ID Lys X17013 1000 1250 NO: 585 (ATCC no. 87482) SSPC3 SEQ ID Thr X04603 1980 5 NO: 586 (ATCC no. 87484) SSPC4 SEQ ID Plum pox virus, AF401296 100 NO: 587 isolated PENN2 (Sppv1) SSPC5 SEQ ID Plum pox potyvirus, X57975 750 NO: 588 mRNA coated protein (Sppv2) SSPC6 SEQ ID Phe M24537 1320 1000 NO: 589 (ATCC no. 87483) SSPC7 SEQ ID Trp K01391 2500 500 NO: 590 (ATCC no. 87485)

[0155] c. 1.: Preparation of the 5 "Spiked controls" of Bacillus subtilis

[0156] The E. coli bacteria with the recombinant plasmids were acquired from ATCC (Rockville, Md. USA) The plasmids (pBluescript II-KS) contained the cloned cDNA of a Bacillus subtilis gene, with cut-off sites for the NotI enzymes at end 5' and BamHI at end 3' and a poly extension (dA) prior to the cut-off site for BamHI.

[0157] After reconstituting and allowing the cells to grow during the night at 37.degree. C. in LB+Ampicillin medium, the plasmid was obtained with the Midipreps kit (Jetstar) following the manufacturer's recommendations. 10 .mu.g of each one of the plasmids was linearized by digestion with 30 U of NotI restriction enzyme, in the presence of 1XNE3 and 1XBSA buffer during 3 hours at 37.degree. C. The linearized plasmids were subjected to extraction with phenol:chloroform:isoamilic alcohol (Ambion), precipitation with 0.1 vol of 3M sodium acetate (Sigma) and 2.5 vol of 100% Ethanol and elimination of salts with 80% Ethanol, following the aforementioned protocol. The DNA obtained was resuspended in 10 .mu.l of RNase-free water.

[0158] Next, the transcripts with sense were synthesized with an in vitro transcription reaction (I.V.T) from 1 .mu.g of plasmid linearized using the MegaScript T3 kit (Ambion) and following the manufacturer's recommendations. The plasmids obtained were purified with the RNeasy Total RNA Isolation Kit (QIAGEN), following the manufacturer's recommendations.

[0159] The quantification, determination of the purity, quality and size of the transcripts obtained were performed following the same methods which are described below for the total RNA.

[0160] c.2. Preparation of the 2 "Spiked Controls" which Represent SPPV Genes

[0161] The recombinant plasmids (Progenika Biopharma) contained the cloned

[0162] cDNA of the two sppvl and sspv2 genes inserted between two PvuII and PstI restriction sites. End 3' of each insert contains a polyadenylation extension.

[0163] JM109 cells were transformed with the plasmids which contained the transcripts. The cells were left to grow in plates with LB+Ampicillin medium at 37.degree. C., the colonies with the transferred cells were selected and they were grown in LB+AMP liquid medium.

[0164] The recovery of the plasmids was performed with the Midipreps Plasmid Purification kit (Qiagen), following the manufacturer's recommendations. 10 .mu.g of each plasmid was linearized with 30 U of the PvuII restriction enzyme. The insert was extracted with phenol:chloroform:isoamilic alcohol (Ambion), precipitation with 0.1 volumes of 7.5 M sodium acetate and 2.5 volumes of 100% ethanol. The salts were eliminated by two washings with 80% ethanol. The DNA obtained was resuspended in 10 .mu.l of Rnase-free water.

[0165] Next, the transcripts with sense were synthesized with 1 .mu.g of plasmid linearized using the T7 MegaScript kit (Ambion) and following the manufacturer's recommendations. The product of the reaction was cleaned with the RNeasy Total RNA Isolation Kit (Qiagen).

[0166] The quantification, measuring of the purity of the transcripts obtained and verification of their size were then performed

[0167] A solution of "Spiked controls" was prepared from the transcripts obtained with different concentrations of each one of those "spiked" (see Table 3), so that they covered the whole range of intensities of the "scanner" reader system (values of intensity which go from 0 to 65,535 in arbitrary units). This solution was added in the same quantity to 5.quadrature. .mu.g of total starting RNA from each sample before starting the process.

[0168] c.3. Design of Probes Representative of Each One of the Transcripts:

[0169] So that the behaviour of the probes was as similar as possible to the probes designed for the genes to be studied, with the Oligo 6.0 programme (M.B.I), those sequences were selected for each "Spiked control" which complied with the same requirements established for the probes of the genes represented (length, GC content, "sense" strand and distance to end 3') and which did not form stable loops (energy less than -7 Kcal/mol). The BLAST tool was applied to the sequences which complied with those requirements and that with less homology with human sequences was chosen.

[0170] After depositing and immobilizing the probes corresponding to the "Spiked controls" on the glass, it was verified: a) that the probes did not hybridrize in non-specific manner with the samples to analyse, b) that all the probes had similar hybridization characteristics, and c) that the signal of intensity obtained from each one of them can be related to the quantity of transcript added to the RNA.

[0171] d) Hybridization Controls

[0172] Snthetic oligonucleotides of DNA with 70 nucleotides (70-mer) were used As hybridization controls, modified at one end with a biotin molecule. These molecules are added in the same quantity to the sample just before hybridization, so that their value only depends on the processes of hybridization, developing and capture of images of the microarray. For each one of these 70-mer oligonucleotides, on the microarray there are several copies of an oligonucleotide with 50 nucleotides in length (50-mer), complementary to the corresponding 70-mer oligonucleotide with which it must hybridize. The 50-mer oligonucleotides which form part of the microarray and which are complementary to 70-mer oligonucleotides which are added to the cRNA before hybridizing are of codes SCN2, SCN3, SCN6, SCN8, SCN11, SCN12 and

[0173] SCN13. To ensure low homology with human sequences, the sequences of these oligonucleotides were obtained from sequences of Arabidopsis thaliana and Tripanosoma brucei. Their characteristics appear in Table 5

TABLE-US-00005 TABLE 5 Oligonucleotides used in the microarray as positive hybridization controls 50-mer oligonucleotide Complementary present in GenBank 70-mer the microarray SEQ ID NO: Source gene code oligonucleotide SCN2 SEQ ID NO: 572 Alpha-1.4- AY026941 C2 fucosyltransferase (FT4-M) from Arabidopsis thaliana SCN3 SEQ ID NO: 573 mRNA of the AJ239128 C3 thioredoxine of Tripanosoma brucei SCN6 SEQ ID NO: 576 mRNA from a supposed AY051079 C6 expression protein of the RBP (complete CDS) from Arabidopsis thaliana SCN8 SEQ ID NO: 578 mRNA from a supposed AY045879 C8 transfer protein of lipids (At1g48750) (complete CDS) from Arabidopsis thaliana SCN11 SEQ ID NO: 581 mRNA from a supposed AY045879 C11 transfer protein of lipids (At1g48750) (complete CDS) from Arabidopsis thaliana SCN12 SEQ ID NO: 582 mRNA from a supposed AY045879 C12 transfer protein of lipids (At1g48750) (complete CDS) from Arabidopsis thaliana SCN13 SEQ ID NO: 583 mRNA of the papain- AF191028 C13 type cysteine endopeptidase XCP2 (complete CDS) from Arabidopsis thaliana

[0174] For the design of the 50-mer oligonucleotides it was verified, in a manner similar to that previously described for the "Spiked controls", that the oligonucleotides to be used did not hybridize in non-specific form with the samples to be analysed, that all the probes had similar hybridization characteristics and that the signal of intensity obtained from each one of them could be related to the quantity of the corresponding 70-mer oligonucleotide added to the cRNA. This made it possible to take as valid the oligonucleotides indicated in Table 5. The SCN4 (SEQ ID NO:574) and SCN9 (SEQ ID NO:579) oligonucleotides, designed in principle to act as hybridization controls, were seen to produce specific hybridization when human cRNA hybridized, for which reason they also appear in the microarray, as if they were probes which represent a human gene, but they are not taken into account as positive hybridization controls. For their part, oligonucleotides SCN1 (SEQ ID NO:571), SCN5 (SEQ ID NO:575), SCN7 (SEQ ID NO:577) and SCN10 (SEQ ID NO:580), which did not hybridize either in non-specific form with the samples, are also present in the microarray as negative hybridization controls, as no oligonucleotide complementary thereto were added to the cRNA.

[0175] For its part, the hybridization controls solution, which contained the 70-mer oligonucleotides complementary to the 50-mer oligonucleotides present in the microarray as positive hybridization controls, was prepared from the corresponding biotinylated 70-mer sequences using a different concentration for each one of them, as shown in Table 6:

TABLE-US-00006 TABLE 6 Composition of the positive hybridization controls solution 70-mer Oligonucleotide Complementary Concentration (pM) added to the 50-mer in the hybridization cRNA SEQ ID NO: oligonucleotide control solution C2 SEQ ID NO: 591 SCN2 750 C3 SEQ ID NO: 592 SCN3 250 C6 SEQ ID NO: 593 SCN6 1500 C8 SEQ ID NO: 594 SCN8 1250 C11 SEQ ID NO: 595 SCN11 2000 C12 SEQ ID NO. 596 SCN12 4500 C13 SEQ ID NO: 597 SCN13 2500

Blanks

[0176] Dimethyl sulfoxide (DMSO) without any probe was used, as this is the solvent wherein the oligonucleotides are found at the time of being deposited on the surface of the microarray.

Description of the Microarray Device

[0177] Twelve replicas of each probe were deposited in different localizations on the surface of a solid support (glass in similar form to a microscope slide) using Microgrid II Spoter (Biorobotics). The 12 replicas of each probe were distributed on the support at random: 6 in the upper area and 6 in the lower area. Aminosylanized glass (Corning) was used as solid support. The moisture and the temperature were controlled throughout the printing process.

[0178] The covalent binding of the probes to the solid supports was carried out by cross-linking by ultraviolet radiation using the "Stratalinker" apparatus (Stratagene).

[0179] The quality control of the production process of the microarrays was the following: a) In each production run a microarray was stained with ethydium bromide which made it possible to analyze the size and form of the points printed. b) Another array of each run was hybridized with an already hybridized cRNA, analysing the hybridization signal, the background noise and the reproducibility of the replicas.

[0180] The characteristics of the array are shown below in Table 7:

TABLE-US-00007 TABLE 7 Characteristics of the microarray Number of genes represented 538 Length of the oligonucleotides 25-55 mer Strand analysed Sense Number of oligonucleotides per gene 1 (except 21 genes which are represented by 2 or 3 different oligonucleotides) Number of replicas of each oligonucleotide 12 Blank DMSO Integrity controls 4 Spiked controls (internal positive controls) 7 Positive hybridization controls 9 Negative controls 11 Total number of points 8192 (32 areas .times. 16 .times. 16) Size of the microarray 25 .times. 75 mm Area spotted 16.38 .times. 17.82 mm Distance between points x- y- axis 360 .mu.m

Treatment of the Samples

Cell Cultures

[0181] Cultures of Jurkat cells (cell line from Leukemia T) and U937 (cell line from promonocytic leukemia) were centrifuged for 10 minutes at 1200 rpm and, after decanting the supernatant, the precipitate was resuspended in RNAlater (Ambion Inc) and it was stored at -80.degree. C. at the time of extraction of the RNA. The RNA was extracted with TRIzol (Gibco-BRL Carlbad, Calif., USA) following the manufacturer's recommendations.

Blood Samples

[0182] The blood samples were directly collected in PAXgene Blood RNA Tubes-PreAnalytix (Qiagen) tubes. 2.5 ml of blood were extracted in each tube and two tubes per individual. The tubes were inverted several times to allow the blood to mix with the stabilizing liquid which the tube contains, and they were stored at -20.degree. C. until the night before RNA extraction.

Extraction of the Total RNA

[0183] The tubes with the sample were incubated at ambient temperature during the night previous to the RNA extraction. The PAXgene Blood RNA kit (Qiagen) was used for the extraction following the manufacturer's recommendations, including the intermediate step of treatment with DNase (RNase-Free DNase Set, Quiagen) in column. The RNA of each extraction tube was eluted in 80 .mu.l of BR5 buffer. The RNA of the two tubes which correspond to each patient was gathered in a single tube.

Purification of the Total RNA

[0184] To ensure that the RNA obtained is free from free from contaminants that can interfere in later labelling reactions, it was purified in the following way: 16 .mu.l (0.1 vol) of 7.5 M sodium acetate (Sigma) and 400 .mu.l (2.5 vol) of 100% ethanol were added to 160 .mu.l of total RNA solution. The solution was mixed in a "vortex" stirrer and it was incubated for 1 hour at -20.degree. C. After 20 minutes of centrifugation at 12,000.times.g at 4.degree. C., the precipitate was washed twice with 500 .mu.l of 80% ethanol and it was resuspended in 35 .mu.l of Rnase-free water. The RNAs obtained were stored at -80.degree. C. until their later use.

Quantification of the Total RNA

[0185] The quantification of the total RNA was carried out by the measurement of the absorbance at 260 nm in a spectrophotometer (DU 65, Beckman Coulter). 2 .mu.l of the total RNA solution were diluted in 98 .mu.l of 1 mM Tris-HCl pH 7.5 and the concentration was estimated (.mu.g/ml) taking into account that 1 Unit of Optical Density at 260 nm corresponds to a RNA concentration of 44 .mu.g/ml.

Determination of the Purity and Quality of the RNA

[0186] The degree of purity was established from the absorbance ratio A260/A280 (nucleic acid/proteins), considering that the RNA is suitable, of "good quality", when the A260/A280 ratio is between 1.9 and 2.1.

[0187] The quality of the total RNA was determined by viewing the RNA after electrophoresis. 500 ng of total RNA were subjected to electrophoresis in 1% agarose gel (FMC) in TAE 1.times. buffer with BrEt (0.5 mg/ml), under a potential differenceof 100V for 25 minutes in AC electrophoresis cuvettes (BioRad). As marker of molecular weights, phage .phi.29 digested with the BamH I restriction enzyme was used. The gels were viewed in a Gel Doc (BioRad) ultraviolet light transiluminator.

Sample Labelling

[0188] The choice of the strand with sense as probe limited the labelling strategy at those approximations which yield an antisense labelled product (complementary to the probe immobilized on the solid support).

cRNA Labelling

[0189] This type of labelling was performed during the course of an amplification process which consists of the use for the synthesis of single-strand cDNA, of an oligo(dT) primer which contains a promoter for the polymerase RNA enzyme of the T7 phage, an enzyme which will be used in the sample amplifications step.

[0190] a.--cDNA synthesis: step wherein DNA (cDNA) complementary to the starting mRNA was synthesized. 5 .mu.g of total RNA was incubated with 2 .mu.l of the "Spiked controls" solution and 100 pmol of T7-(dT)24 (Genset Corp) primer in final volume of 12 .mu.l during 10 minutes at 70.degree. C. in a thermoblock, the mixture was cooled on ice and 4 .mu.l of 5.times. First Strand Buffer (Gibco BRL Life Technologies), 0.1M 2 .mu.l DTT (Gibco BRL Life Technologies), 1 .mu.l dNTP mix 10 mM (Gibco BRL Life Technologies) and 1 .mu.l of SuperScript II RNase H RT (200 OR/.mu.l) (Gibco BRL Life Technologies) were added. After 1 hour of incubation in a bath equipped with a thermostat (Selecta) at 42.degree. C., the reaction was cooled on ice.

[0191] b.--Double chain DNA synthesis (dsDNA): a double chain of DNA was synthesized from the cDNA synthesized in the previous step. To 20 .mu.l of previous reaction were added 91 .mu.l of Rnase-free water, 30 .mu.l of "Second Strand Reaction buffer" (Gibco BRL Life Technologies), 3 .mu.l 10 mM dNTPs (Gibco BRL Life Technologies), 10 U E. coli DNA Ligase (Gibco BRL Life Technologies), 40 O E. coli DNA polymerase I (Gibco BRL Life Technologies), 2 U E. coli RNase H (Gibco BRL Life Technologies) in a final volume of 150 .mu.l. The reaction was incubated in a thermoblock at 16.degree. C. for 2 hours. Next, 10 U of T4 DNA Polymerase (Gibco BRL Life Technologies) were added and the mixture was incubated at 16.degree. C. for 5 minutes. To stop the reaction, 10 .mu.l of 0.5 M EDTA were added.

[0192] c.--Purification of the dsDNA: To eliminate possible remains of reaction products which may interfere in later labelling reactions, the DNA obtained through phenol/chloroform extraction and later precipitation was purified. To 162 .mu.l of previous reaction 162 .mu.l of phenol: chloroform: isoamilic alcohol solution (25:24:1) (Ambion) were added. It was centrifuged for 2 min at 12,000.times.g in a centrifuge at ambient temperature, the upper aqueous phase was collected. To this upper phase 0.5 volumes of 7.5M ammonium acetate (Sigma Chemical) and 2.5 volumes of 100% ethanol cooled to -20.degree. C.) were added. After stirring with "vortex" to mix well the components and centrifugation for 20 minutes at 12000.times.g at ambient temperature, the supernatant was eliminated and the precipitate was washed twice with 80% ethanol. The DNA obtained was resuspended in 10 .mu.l of RNase-free water and it was concentrated in a "Speed-Vac" concentrator to a volume of 2 .mu.l. This DNase was stored at -20.degree. C. until its later use.

[0193] d.--Synthesis and labelling of the cRNA: This reaction was carried out in a volume of 20 .mu.l and using the T7 Megascript kit (Ambion), following the manufacturer's instructions and incorporating nucleotides modified with biotin, Bio-11-CTP and Bio-11 UTP (Perkin Elmer) in non-modified nucleotide/modified nucleotide ratio of 1:3. The reaction was incubated during 5 h and 15 minutes in a bath with thermostat (Selecta) at 37.degree. C., stirring the reaction every 45 minutes. After this incubation, 1 .mu.l of DNase was added and it was incubated for 30 min at 37.degree. C.

[0194] e.--Purification of the biotinylated cRNA: The biotinylated cRNA was purified with the RNeasy Total RNA Isolation Kit (Qiagen) following the manufacturer's instructions. The biotinylated cRNAs obtained were eluted in a volume of 80 .mu.l and they were stored at -80.degree. C. until its later use.

[0195] The quantity, purity and quality of the cRNA obtained were determined following the same methods described for the total RNA.

[0196] The cRNA was stored at -80.degree. C. until its later use.

Fragmentation of the Biotinylated cRNA

[0197] 10 .mu.g of biotinylated cRNA were fragmented in the presence of 5.times. (200 mM Tris-acetate, pH 8.1, 500 mM HOAC, 150 mM MgOAc) fragmentation buffer during 35 minutes at 94.degree. C. in a thermoblock. It was verified that the fragmentation reaction had been carried out by viewing 1 .mu.l of fragmentation solution in electrophoresis on 1% agarose gel.

Hybridization of the cRNA Labelled with the Probes of the Microarray

[0198] In this step the labelled genetic material were placed in contact with the probes immobilized on the solid support.

[0199] 10 .mu.l of the hybridization control solution were added to the biotinylated and fragmented cRNA solution and the mixture was incubated for 3 min at 95.degree. C. to denature the possible secondary structures. After incubation, the mixture was immediately taken to ice to prevent the possible renaturing of the sample.

[0200] The hybridization was carried out for 6 hours at 42.degree. C. in the Ventana Discovery automatic hybridization station (Ventana Medical Systems). The hybridization and washing buffers were supplied by Ventana Medical System. The microarrays were automatically stained in the hybridization station with streptavidin conjugated with Cy3 (Amersham Biosciences) using the manufacturer's recommendations.

Capture of Images and Quantification of the Microarrays

[0201] After the hybridization and developing, the images of the microarrays were identified and analysed by the ScanArray 4000 confocal fluorescent scanner (Perkin Elmer) equipped with a laser for the green (543 nm to excite the fluorophore Cy3). The "software" used was ScanArray 3.1. The use of the computer programme QuantArray 3.0 (Perkin Elmer) provided the absolute values of the intensity of hybridization and background noise in accordance with the light emitted by the Cy3 in each probe in an Excel format.

Data Analysis: Preliminary Processing

[0202] In first place, the value of the background noise were subtracted from the values of absolute intensity of all the oligonucleotides. To do this, the values of absolute intensity and the values of background noise, which the programme used to convert the signals of the fluorophore returns, automatically, were used for each one of the microarray points: the corresponding in tensity value is obtained from the zone which has been defined as point and the value of the background noise is obtained from the zone situated around the point.

[0203] Next, the average level of hybridization intensity of each one of the oligonucleotides of the microarray was calculated from the trimmed mean of the intensities of the 12 replicas of each one of the oligonucleotides. To do this, before calculating the average, the upper and lower values of the distribution points of hybridization signals obtained with each one of the replicas of the same oligonucleotide have to be eliminated. The calculation was performed using the Excel programme from Microsoft and, specifically, the TRIMMEAN function thereof, wherein the "percentage" parameter was set at 0.2, which supposes fixing the percentage of values eliminated in 20% of the upper values and 20% of the lower values; the function rounds up the number of data points excluded to the closest multiple of 2.

[0204] In last place, and to be able to determined the validity of the hybridization, it is necessary that a series of established criteria are met: 1) the ratio between the average intensity and the aver age background of all the oligonucleotides of the chip is greater than 10; 2) the value of the average coefficient of variation (standard deviation of the replicas compared with the average of the replicas) of all the replicas of oligonucleotides of the chip should be less than 0.3; 3) the average value of the negative control should be less than 2.5 times the value of the DMSO medium; 4) a signal should be obtained both in the hybridization controls and in the exogenous internal positive controls (Spiked controls).

[0205] The data analysis was performed in R, version 1.9.1. R is a programming language wherein both classical and modern statistical techniques can be applied (R Developmental Core Team, 2004; http://www.R-project.org), which has a series of functions stored in packages for the handling, calculation and graphic representation of data (Venables et al., 2004). There are hundreds of packages written by different authors for R, with special statistical functions or which permit the access and handling of data and are available for downloading from the websites of CRAN (http://cran.r-project.org/) or Bioconductor (http://www.bioconductor.org). In some specific cases, the SPSS commercial statistical analysis software was used (Chicago, USA).

EXAMPLES

Example 1

Results Obtained on Using the Microarray Device with Samples of U937 Vs Jurkat Cells

[0206] In order to know if the device permits differentiating two cells lines hybridized in 10 microchips: 5 samples of biotinylated cRNAs synthesized following the optimized working protocol, obtained from RNA of U937 cells (cell line from promonocytic leukemia) and 5 samples of biotinylated cRNAs obtained from RNA of Jurkat cells (cell line from T Leukemia).

[0207] The initial steps of preliminary processing of the data and validation of the hybridization mentioned previously in the "Data analysis: Preliminary processing" section were carried out and then the data was normalized and filtered: [0208] Data normalization. The "variance stabilization normalization" method was used, available in the "vsn" package in R. There are different packages available on the Internet for R, with special statistical functions or which permit the access and processing of data and are available for downloading from CRAN (http://cran.r-project.orq/) or Bioconductor (http://www.bioconductor.orq) [0209] ata filtering. Two filtering operations have been carried out with the "Filterfun" function of the of the "Genefilter" filter in R. The genes which did not pass any of the two filters were not used in the data analysis. The filters carried out were: [0210] Filtering to exclude genes with an intensity value close to the DMSO. This filter made it possible to work with genes with an intensity value minus average background noise greater than 550 arbitrary units (approximately 2 times the value of the DMSO). [0211] Filtering to exclude genes with minimum intensity variation throughout the samples. Genes were worked with an interquartile range of normalized intensity throughout samples greater than 0.3.

[0212] The data filtering left 83 probes which constituted the working list. With them a grouping was made of the non-supervised samples, which are those groupings wherein the structure of the data is not previously known, the system learning how the data are distributed among classes based on a distance function. A tree or hierarchical group was obtained with the grouping, wherein the samples are grouped in accordance with their similarity in the expression of certain genes, those corresponding to the oligonucleotides of the working list, so that the closest samples are those which have a similar expression profile. The grouping was performed with the hclust function of the stats package in R. The non-supervised analysis of the 10 samples produced their separation in two groups or main branches in accordance with the cell type whereto the samples belong: a group contains the 5 hybridizations carried out from U937 cells and the other group contains the 5 hybridizations carried out from Jurkat cells. The resulting tree of this non-supervised grouping is shown in part A of FIG. 1.

[0213] Next, to find out if there were statistically significant differences between the two groups of samples, the "Step-down maxT multiple testing methods" method (maxT) was used, which is an application of the mt.maxT function of the multtest package of the software in R from Bioconductor, which applies a statistical test and carries out a strong control over the rate of false positives. To this function, the following should be provided:

[0214] a) Values on which one wants to apply the statistical tests, in this case, on the normalized values of the 83 oligonucleotides which passed the filters

[0215] b) Groups of which one wants to seek differences, in this case the 5 samples of Jurkat cells against the 5 samples of cells U937

[0216] c) Number of permutations one wants to perform. In this case, 100,000 permutations are carried out.

[0217] d) By default, Welch's test was chosen to specify the statistical tool to be used to test the hypothesis of non-association between the variables and the class labels.

[0218] The application of this analysis with a value of p<0.001 provided a list of 69 statistically significant probes between the two groups, which are the following: [0219] SG12, SG20, SG23, SG24, SG38, SG39, SG45, SG49, SG53, SG59, SG60, SG62, SG76, SG78, SG89, SG92, SG94, SG102, SG474, SG478, SG487, SG114, SG120, SG140, SG142, SG145, SG150, SG154, SG158, SG174, SG175, SG194, SG195, SG211, SG230, SG231, SG235, SG260, SG264, [0220] SG266, SG268, SG270, SG272, SG282, SG294, SG308, SG311, SG330, SG332, [0221] SG333, SG339, SG344, SG364, SG403, SG423, SG434, SG456, SG506, SG513, SG514, SG515, SG524, SG533, SG538, SG541, SG559

[0222] Once the statistically significant genes to distinguish between the two groups of samples are known (which would be the genes corresponding to the probes identified as statistically significant) the supervised grouping was carried out of the samples in accordance with the intensity of the signal of the 69 statistically significant probes obtained. The term "supervised", applied to a grouping, makes reference to the fact that the data structure is previously known, which makes it possible to use the prior information; with this, after a training process which allows the system to learn to distinguish between classes, it is possible to use the network to assign new members to the predefined classes. In this case, the supervised grouping of the samples in accordance with the intensity of the signal obtained with the 69 statistically significant probes obtained, is again a tree which is divided in two main branches in accordance with the cell type to which the samples belong. The tree obtained with the supervised grouping is shown in part B of FIG. 1.

Example 2

Results Obtained on Using the "Array" Device with Samples from Healthy Subjects Vs U937 and Jurkat Cells

[0223] The expression of 5 samples of U937 cells and 5 samples of Jurkat cells was compared with the expression of 10 samples from total blood from healthy subjects. In a manner similar to that carried out in Example 1, the initial data processing steps, validation of the hybridizations, normalization and filtering were carried out. A total of 180 genes passed the filtering processes. The non-supervised grouping of the samples (carried out with the hclust function of the stats package of R applying Pearson's correlation) in accordance with the expression of the 180 genes, provided a tree with two main branches: one branch contains all the samples from cell cultures and the other branch contains all the samples from total blood from healthy subjects, which demonstrates that the tool is capable of finding expression differences. The tree obtained after making this non-supervised grouping is shown in part A of FIG. 2.

[0224] The maxT test (p<0.001) to find genes with statistically significant differences between the samples from U937 and Jurkart cell cultures and the 10 samples from total blood of healthy subjects was performed. The statistical analysis provided a list of 131 probes with statistically significant differences between both groups of samples. They are the following:

SG1, SG4, SG7, SG8, SG10, SG13, SG15, SG16, SG17, SG18, SG19, SG20, SG26, SG29, SG30, SG34, SG36, SG39, SG42, SG44, SG49, SG51, SG52, SG58, SG64, SG65, SG67, SG76, SG77, SG80, SG84, SG86, SG89, SG92, SG93, SG94, SG98, SG99, SG101, SG102, SG107, SG463, SG464, SG474, SG475, SG485, SG487, SG466, SG467, SG471, SG472, SG473, SG120, SG129, SG138, SG141, SG144, SG145, SG147, SG158, SG163, SG164, SG176, SG185, SG186, SG197, SG207, SG208, SG217, SG227, SG231, SG265, SG266, SG277, SG278, SG283, SG285, SG299, SG307, SG308, SG311, SG313, SG318, SG319, SG328, SG333, SG336, SG342, SG344, SG357, SG361, SG376, SG384, SG389, SG395, SG398, SG403, SG404, SG407, SG416, SG420, SG423, SG430, SG436, SG446, SG455, SG461, SG489, SG491, SG492, SG493, SG498, SG500, SG504, SG505, SG506, SG514, SG516, SG517, SG520, SG526, SG530, SG533, SG538, SG545, SG547, SG554, SG555, SG558.

[0225] The grouping of the 20 samples, in accordance with the expression of the statistically significant probes found, gave rise again to a tree with two main branches, one corresponding to the samples from cell cultures and another corresponding to the samples from healthy individuals. Said grouping appears in part B of FIG. 2.

Example 3

Results Obtained with Samples from Patients with Chronic Lymphatic Leukemia (CLL) Vs U937 and Jurkat Cells

[0226] The expression profiles were compared of samples from U937 and Jurkats cell cultures with 26 samples from total blood of subjects with CLL.

[0227] The samples underwent preliminary processing of the data, they were normalized and filtered in a manner analogous to those used in Examples 1 and 2 and a total of 236 probes passed through the filters. The non-supervised grouping of the samples in accordance with the expression of the probes which passed through the filters showed a tree with two main branches: one which contained the samples of cell cultures and the other the CLL samples. Said tree is shown in part A of FIG. 3.

[0228] The maxT test (p<0.001) to find genes with statistically significant differences between the two groups of samples was carried out. This analysis provided a list of 120 probes. They are the following: SG2, SG4, SG8, SG10, SG13, SG15, SG16, SG19, SG20, SG23, SG26, SG28, SG31, SG34, SG36, SG39, SG48, SG58, SG60, SG65, SG76, SG77, SG84, SG89, SG94, SG9, SG97, SG99, SG102, SG106, SG107, SG463, SG464, SG474, SG475, SG481, SG465, SG485, SG487, SG466, SG467, SG471, SG473, SG115, SG116, SG117, SG120, SG129, SG134, SG135, SG138, SG139, SG141, SG145, SG158, SG161, SG163, SG176, SG178, SG185, SG207, SG208, SG210, SG217, SG227, SG231, SG237, SG264, SG272, SG277, SG281, SG283, SG286, SG294, SG298, SG299, SG307, SG308, SG319, SG328, SG330, SG333, SG336, SG342, SG344, SG345, SG347, SG361, SG384, SG389, SG395, SG404, SG407, SG416, SG423, SG428, SG430, SG432, SG434, SG444, SG446, SG453, SG458, SG459, SG491, SG498, SG507, SG508, SG511, SG517, SG518, SG522, SG526, SG530, SG533, SG538, SG541, SG554, SG558, SG561.

[0229] The grouping of the 30 samples in accordance with the expression of the 120 statistically significant probes found again gave rise to a tree with two main branches, one corresponding to the samples from cell cultures and another corresponding to the samples from healthy individuals. Said grouping appears in part B of FIG. 3.

Example 4

Results Obtained with Samples from Healthy Subjects Vs Patients with Chronic Lymphatic Leukemia (CLL)

[0230] 68 hybridizations which met the quality criteria from 68 samples of different healthy subjects and with clinical diagnosis of CLL were divided in 2 groups: Training Group used to obtain the functions of the classifier and Test Group, used to test the classifier obtained. The Training group was composed of 30 samples (10 from healthy subjects and 20 from CLL subjects) and the Test Group was composed of 38 samples (5 samples from healthy subjects and 33 samples from subjects with CLL).

[0231] To obtain the classification function, the results obtained from the hybridizations of the Training group were worked with. The steps carried out to obtain the classification function were: [0232] Data normalization. The "variance stabilization normalization" method, available in the "vsn" package in R, was used. [0233] Data filtering. Two filtering operations have been carried out with the "Filterfun" function of thee "Genefilter" package in R. The genes which did not pass any of the two filters were not used in the data analysis. From the 588 oligonucleotides of the chip, 224 passed through the 2 filters and constituted the working list. [0234] 2. Filtering to exclude genes with an intensity value close to the DMSO. This filter made it possible to work with genes with an intensity value minus average background noise greater than 550 arbitrary units (approximately 2 times the value of the DMSO) in more than 25% of the samples (7 samples) which compose the Training group. [0235] 3. Filtering to exclude genes with minimum intensity variation throughout the samples. Genes were worked with which had an interquartile range of normalized intensity throughout samples greater than 0.3.

[0236] Two classification systems are used:

[0237] 4.1.--Construction of a Classification System with PAM.

[0238] To identify groups of genes which best characterize each type of sample and verify the classification rate of these groups of genes Prediction Analysis for Microarrays (PAM) was used, available as "pamr.sup.a" package in R. It is a statistical technique which identifies a group of genes which best characterizes a predefined class and uses this group of genes to predict the class whereto new samples belong. PAM uses a modified version of the "nearest centroids" classification method (Tibshirani et al., 2002) called "Nearest Shrunken Centroids". A validation called "10 fold cross validation" was performed, which consists of constructing the model with 90% of the samples and an attempt is made to predict the class of 10% of the samples which have not intervened in the construction of the model. This method is repeated 10 times and the classification error of 10% of the samples is added to calculate the overall error. This error reflects the number of badly classified samples (Bullinger et al., 2005).

[0239] 4.1.1. Construction of the model. From the filtered and normalized data of the 30 samples which compose the Training group, attributing in an arbitrary form the Healthy Group to group 0 and the CLL Group to group 1, performing the 10 cross-validations and with a threshold value of Delta 3.1. The model obtained was formed by the following oligonucleotides: SG459, SG428, SG507, SG508, SG117, SG237. The coefficients of the classifier corresponding to each one of these oligonucleotides are shown below in Table 8:

TABLE-US-00008 TABLE 8 Coefficients of the PAM classifier id Value 0 Value 1 [1,] SG459 -0.4344 0.2172 [2,] SG428 -0.146 0.073 [3,] SG507 -0.1111 0.0555 [4,] SG508 -0.1044 0.0522 [5,] SG117 -0.1003 0.0502 [6,] SG237 -0.0539 0.027

[0240] 4.1.2. Validation of the PAM classifier. The cross-validation of the samples which compose the Training group correctly classified 28 of the 30 samples.

[0241] From the filtered and normalized data of the 38 samples which compose the Test Group, probability values p were obtained belonging to group 0 (healthy group) or group 1 (CLL group). The greater the value of p, the greater the probability of belonging to that group. It has been considered that the values greater than 0.5 indicate belonging to that group. The values of p obtained for each sample are indicated in Table 9.

TABLE-US-00009 TABLE 9 Probability values obtained with the PAM classifier for the Test Group Sample p (Group 0) p (Group 1) S229 0.8031905 0.1968095 S231 0.7403173 0.2596827 S232 0.8810574 0.1189426 S233 0.7973159 0.2026841 S251 0.8714224 0.1285776 CLL166 0.3764637 0.6235363 CLL184 0.1278230 0.8721770 CLL132 0.2081423 0.7918577 CLL210 0.3248082 0.6751918 CLL213 0.3536033 0.6463967 CLL214 0.2705277 0.7294723 CLL221 0.3650277 0.6349723 CLL208 0.2323872 0.7676128 CLL225 0.4034316 0.5965684 CLL236 0.4893545 0.5106455 CLL240 0.3807527 0.6192473 CLL168 0.1616066 0.8383934 CLL172 0.2002317 0.7997683 CLL174 0.1601147 0.8398853 CLL175 0.6009558 0.3990442: .fwdarw.Only badly classified sample CLL177 0.1634185 0.8365815 CLL179 0.2300440 0.7699560 CLL181 0.2177406 0.7822594 CLL182 0.3450880 0.6549120 CLL164 0.2590083 0.7409917 CLL159 0.3688586 0.6311414 CLL142R 0.2111712 0.7888288 CLL105 0.2962797 0.7037203 CLL107 0.3764637 0.6235363 CLL109 0.3525788 0.6474212 CLL112 0.2059187 0.7940813 CLL151 0.2951067 0.7048933 CLL158 0.1932882 0.8067118 CLL169 0.3525937 0.6474063 CLL171 0.1495153 0.8504847 CLL178 0.2260191 0.7739809 CLL111 0.2951168 0.7048832 CLL155 0.2832151 0.7167849

[0242] With this model 37 of the 38 samples of the Test Group are correctly classified: all the samples corresponding to healthy individuals (those whose name is headed by the letter "S") have a probability greater than 0.5 of belonging to group 0, whilst all the samples corresponding to individuals suffering from CLL (which are the samples whose name starts with letters "CLL") minus one have a probability greater than 0.5 of belonging to group 1.

[0243] 4.2.--Construction of a Classification System with Logistical Regression.

[0244] 4.2.1.--Selection of genes with statistically significant differences among healthy and CLL (Training group). From the filtered and normalized data as has been previously described, the "Step-down maxT multiple testing methods" method (maxT) was used for the selection of genes with significant differences, which is an application of the mt.maxT function of the multtest package of the software in R from Bioconductor, which applies a statistical test and carries out a strong control over the rate of false positives. The application of this statistical test, with a value of p<0.001, to the 224 oligonucleotides which passed through the filters, produced a list of 7 oligonucleotides: SG117, SG428, SG459, SG461, SG493, SG507, SG508.

[0245] The steps used to obtain the list of 7 significant genes among healthy and CLL were: [0246] Method which makes permutations and adjusts the values of p resT<-mt.maxT(exprs(224 oligonucleotides which have passed through the filters and normalized of the training group, Types of samples in the training group, test="t", B=100000): mt.maxT function which through permutations adjusts the probability values (signification) which entails a strong control of the rate of false positives.

[0247] To this function the following should be provided:

1. Values on which one wants to apply the statistical tests, in this case, on the normalized values of the 83 oligonucleotides which passed through the filters 2. Groups of which one wants to seek differences, in this case the 5 samples of Jurkat cells against the 5 samples of cells U937 3. Number of permutations one wants to perform. In this case, 100,000 permutations are carried out. 4. By default, Welch's test was chosen as statistical test.

[0248] The statistically significant genes at a level of p<0.001 were selected by this test and a number of 7 was obtained.

[0249] 4.2.2.--Obtainment of the classification function with SPSS. By logistical regression from the normalized values of the 7 statistically significant oligonucleotides obtained from the 30 samples which compose the Training group and assigning in arbitrary manner group 0 to the healthy samples and group 1 to the CLL samples, the values of the classification function were obtained. The coefficients corresponding to each oligonucleotide were those which are shown below in Table 10:

TABLE-US-00010 TABLE 10 Coefficients of the classification function Calculated by logistical regression Oligonucleotide Coefficients (Coeff) SG117 2.44756372 SG428 7.38657611 SG459 23.1465464 SG461 43.6287742 SG493 -19.3978182 SG507 -2.80282646 SG508 49.5345672 Constant -719.241486

[0250] From these coefficients, for each sample i a value x.sub.i is calculated as follows:

x.sub.i=Constant+(Coeff ohle0009*Imn.sub.iSG117)+(Coeff SG428*Imn.sub.iSG428)+(Coeff SG459*Imn.sub.i SG459)+(Coeff SG461*Imn.sub.iSG461)+(Coeff SG493*Imn.sub.i SG493)+(Coeff SG507*Imn.sub.iSG507)+(Coeff SG508*Imn.sub.iSG508).

[0251] where Imn.sub.i is the average value of normalized intensity of the sample i.

[0252] From the value x.sub.i a value of probability (p.sub.i) is calculated. The closer the value of p is to 0, the greater the probability of belonging to the group of healthy subjects (assigned as group 0) and the closer the value of p is to 1, the greater the probability there is of the sample belonging to the group of CLL subjects (assigned as group 1). The formula used to determine the value of p is:

p.sub.i=1/(1+e.sup.-xi).

[0253] As is shown in Table 11, the function obtained correctly classified the 30 samples belonging to the training group. The closer to 0, the greater the probability that it is healthy and the closer to 1 the greater probability of CLL.

TABLE-US-00011 TABLE 11 Classification table.sup.a Prognosis EVOL Correct Observed 0 1 percentage Step 1 EVOL 0 10 0 100.0 1 0 20 100.0 Overall percentage 100.0 .sup.aThe cut-off value is ,500

[0254] 4.2.3. Validation of the system classifier.--From the filtered and normalized filters as detailed above, the Imn.sub.i values were obtained of the 7 oligonucleotides which compose the classifier of each one of the 38 samples which compose the Test Group.

[0255] Results of the validation of the system classifier. Below, tables are shown wherein the Imn.sub.i value is obtained of each one of the 7 oligonucleotides included in the classifier and the values of x.sub.i and p.sub.i calculated according to the formulas previously described, obtained for each one of the 38 samples of the Test Group. The samples which begin with S correspond to healthy subjects and the samples which start with CLL are from CLL subjects. 37 out of 38 samples are correctly classified. Only sample CLL175, for which a value of pi=0 is obtained is incorrectly classified.

TABLE-US-00012 TABLE 12 Results obtained with the Test Group by the classification function obtained by logistical regression lmn.sub.i S229 S231 S232 S233 S251 CLL166 CLL184 CLL132 CLL210 CLL213 CLL214 SG117 4.89 5.17 5.14 5.33 5.37 6.17 7.45 7.05 7.06 6.88 6.86 SG428 4.82 4.80 4.52 4.69 4.52 5.74 6.97 6.46 6.66 6.08 6.49 SG459 6.50 6.95 6.10 6.59 5.96 8.11 9.04 8.71 8.13 8.15 8.40 SG461 6.47 6.41 6.44 6.43 6.05 6.35 7.22 6.99 6.75 6.75 7.04 SG493 7.20 7.31 7.02 7.16 6.83 7.53 7.69 7.35 7.43 7.35 7.57 SG507 8.32 7.82 7.26 7.77 7.47 9.11 9.82 9.32 9.19 8.49 9.18 SG508 6.67 6.82 6.34 6.82 6.81 7.79 8.71 7.80 7.55 7.66 7.68 x.sub.i -71.35 -56.83 -93.68 -61.26 -86.57 17.23 129.51 70.11 33.93 38.26 55.19 p.sub.i 0.00 0.00 0.00 0.00 0.00 1.00 1.00 1.00 1.00 1.00 1.00 lmn.sub.i CLL221 CLL208 CLL225 CLL236 CLL240 CLL168 CLL172 CLL174 CLL175 CLL177 SG117 7.00 7.42 6.91 6.40 6.76 7.34 7.32 7.40 5.32 7.72 SG428 6.40 6.98 6.00 6.24 6.09 6.77 6.16 7.49 4.85 6.38 SG459 7.93 8.54 8.01 7.55 8.19 8.94 8.86 8.69 7.72 8.78 SG461 6.77 7.18 6.89 6.79 6.54 6.72 7.02 7.18 5.98 6.86 SG493 7.14 7.92 7.72 7.47 6.73 7.97 7.96 8.45 7.16 8.05 SG507 9.00 8.98 8.41 8.74 8.80 9.53 9.67 10.09 8.76 9.76 SG508 7.50 7.43 7.22 7.36 6.90 8.08 7.38 7.81 6.43 7.94 x.sub.i 31.80 50.30 12.52 8.94 3.77 67.59 39.95 63.19 -75.92 59.42 p.sub.i 1.00 1.00 1.00 1.00 0.98 1.00 1.00 1.00 0.00 1.00 lmn.sub.i CLL179 CLL181 CLL182 CLL164 CLL159 CLL142R CLL105 CLL107 CLL109 CLL112 SG117 6.89 6.92 6.14 8.03 6.98 6.80 6.52 6.17 6.79 7.31 SG428 6.32 6.22 5.64 5.40 5.55 5.94 6.05 5.74 5.81 6.52 SG459 8.52 8.71 8.35 8.54 8.00 8.87 8.32 8.11 8.20 8.77 SG461 6.83 6.95 6.87 6.96 6.63 7.07 6.72 6.35 6.66 6.80 SG493 7.99 7.92 7.71 7.73 7.49 7.96 7.79 7.53 7.70 7.99 SG507 9.40 9.53 9.37 8.86 9.34 9.49 9.49 9.11 8.89 9.41 SG508 8.17 8.18 7.37 7.80 7.81 7.97 7.75 7.79 7.46 7.69 x.sub.i 62.78 73.52 19.76 53.03 28.34 68.92 33.36 17.23 16.00 45.86 p.sub.i 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 lmn.sub.i CLL151 CLL158 CLL169 CLL171 CLL178 CLL111 CLL155 SG117 6.51 7.26 6.79 7.76 6.62 6.51 6.90 SG428 6.14 6.17 5.81 5.96 5.97 6.14 5.44 SG459 8.40 8.81 8.20 9.18 8.77 8.40 8.44 SG461 6.64 7.01 6.66 7.10 6.79 6.64 6.71 SG493 8.00 8.12 7.70 8.03 8.05 8.00 7.91 SG507 9.11 9.36 8.89 9.52 9.36 9.11 9.35 SG508 7.87 8.29 7.46 7.99 8.06 7.87 8.23 x.sub.i 35.32 81.12 16.00 79.33 57.33 35.32 53.92 p.sub.i 1.00 1.00 1.00 1.00 1.00 1.00 1.00

[0256] A third group of 40 samples was formed. To do this, replicas of hybridization or of labelling were used (the samples whose name begins with S and Strans are samples from people considered healthy and those which start with CLL are samples from patients with chronic lymphatic leukemia). This group of samples was used to validate the classification system. The data were normalized as has been previously described. The results of the classification are shown in the Table 13. 40 out of the 40 samples are correctly classified.

TABLE-US-00013 TABLE 13 Results obtained in the validation of the classification function obtained by logistical regression lmn.sub.i S120.7 S120.14 Strans.3 Strans.4 S150.2 S228.6 S229.7 CLL142.8 CLL147.9 S120.7 SG117 5.22 5.40 5.41 4.95 5.47 6.05 5.34 7.06 5.39 5.22 SG428 4.95 4.64 4.29 4.20 5.01 3.89 5.07 6.31 5.59 4.95 SG459 6.39 6.14 5.46 4.98 7.14 5.72 6.23 9.01 8.56 6.39 SG461 5.73 6.16 6.23 6.38 6.72 6.01 6.39 7.02 7.05 5.73 SG493 6.78 7.05 5.03 5.15 6.95 6.37 6.22 7.87 8.07 6.78 SG507 7.83 7.62 5.83 5.78 8.17 7.26 7.85 9.74 8.82 7.83 SG508 6.42 6.46 6.90 4.56 6.62 6.70 6.71 8.19 8.17 6.42 x.sub.i -107.44 -99.01 -48.21 -172.85 -40.21 -93.50 -56.20 85.27 64.43 -107.44 p.sub.i 0.00 0.00 0.00 0.00 0.00 0.00 0.00 1.00 1.00 0.00 lmn.sub.i CLL148b.10 CLL148c.11 CLL111.12 CLL163.13 CLL108.15 CLL160.1 CLL160.2 CL L187.5 SG117 6.98 6.83 6.54 6.16 6.87 7.74 7.71 7.58 SG428 6.64 6.63 6.17 5.61 6.56 5.92 5.69 7.24 SG459 9.13 9.29 8.44 8.33 8.55 8.29 8.25 9.01 SG461 7.16 7.48 6.67 6.61 6.86 7.21 7.25 7.35 SG493 7.70 7.89 8.05 7.92 7.67 7.66 7.58 8.05 SG507 9.90 10.02 9.16 9.16 9.66 8.88 8.93 9.99 SG508 8.27 8.45 7.92 7.86 7.89 7.57 7.51 8.30 x.sub.i 102.70 125.01 39.43 28.30 58.29 51.63 48.76 109.23 p.sub.i 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 lmn.sub.i CLL197.14 CLL198.15 CLL199.16 CLL200.17 CLL201.18 CLL20_LE CLL208.1 CLL210.2 SG117 6.66 6.13 7.14 7.58 7.97 6.67 7.40 7.11 SG428 5.98 5.10 6.71 6.72 7.54 5.97 6.77 6.71 SG459 8.35 7.97 8.34 8.99 9.30 8.26 8.34 8.19 SG461 6.76 6.36 7.02 7.26 7.35 6.83 6.99 6.79 SG493 7.80 7.27 7.96 8.09 8.39 7.53 7.44 7.48 SG507 9.38 8.71 9.58 9.87 10.23 9.04 8.65 9.26 SG508 8.00 7.48 7.72 8.64 8.76 7.17 7.09 7.61 x.sub.i 48.40 0.40 48.33 116.75 134.69 14.31 29.64 39.38 p.sub.i 1.00 0.60 1.00 1.00 1.00 1.00 1.00 1.00 lmn.sub.i CLL225.6 CLL236.7 CLL240.8 CLL184b.9 CLL184C.10 CLL208.1 CLL213.5 CLL214.6 SG117 7.35 6.54 6.80 7.12 7.06 7.24 6.97 7.06 SG428 6.46 6.43 6.11 6.97 6.36 6.34 5.80 6.45 SG459 8.20 7.60 8.24 8.37 8.37 8.07 8.17 8.35 SG461 6.90 6.85 6.58 7.05 6.73 6.53 6.43 6.79 SG493 7.28 6.90 6.77 7.40 7.17 7.59 7.47 7.63 SG507 8.45 8.55 8.85 9.22 8.88 8.08 8.61 9.13 SG508 7.13 7.29 6.93 8.21 8.01 7.14 7.77 7.72 x.sub.i 25.36 22.47 7.52 88.13 65.29 0.80 26.04 44.00 p.sub.i 1.00 1.00 1.00 1.00 1.00 0.69 1.00 1.00 lmn.sub.i CLL221.7 CLL193.1 CLL193.2 CLL197.1 CLL197.2 SG117 6.97 6.76 6.73 6.22 6.00 SG428 6.47 7.26 7.22 5.81 5.71 SG459 7.98 8.28 8.27 8.26 8.07 SG461 6.60 7.18 7.17 6.78 6.62 SG493 7.66 7.95 7.93 7.79 7.85 SG507 9.23 9.01 9.04 8.86 8.72 SG508 7.74 7.68 7.77 7.55 7.64 x.sub.i 27.46 56.71 60.37 23.63 14.87 p.sub.i 1.00 1.00 1.00 1.00 1.00

Example 5

Results Obtained with "Stable" CLL Samples Compared with "Progressive" CLL Samples

[0257] "CLL-stable type" (S) samples are considered those of patients who have had stable CLL for over 5 years and "CLL-progressive type" (P) samples are considered the samples of patients classified as stable at the time of diagnosis and whose disease has progressed in less than one year.

[0258] In total 6 S samples and 6 P samples were analysed. The 12 samples were collected at the time of diagnosis, without clinical differences between them, but after one year, 6 of those patients had progressed. The 12 hybridizations have passed the aforementioned quality criteria.

[0259] Stable samples: E142R, E148, E156, E163, E164, E193

[0260] Progressive samples: P111, P105, P177, P158, P157 and P197.

[0261] All the data analysis was performed in R version 1.9.1.

[0262] Data normalization. In this case, and to avoid the significant genes obtained are due to a real difference between samples and not to the effect of normalization, the data were normalized in two different forms ("variance stabilization normalization" (vsn) and by robust quantiles) and the same statistical analysis was performed with each one of the normalizations. [0263] Statistical analysis with normalized data by "variance stabilization normalization". The list of statistically significant genes was obtained from a Welch's test with the mt.maxT function of the multtest package in R, with a value of p<0.05 without adjusting, i.e. without performing any control on the false positives and produced a list of 29 genes with stat istically significant differences between the CLL-stable type and CLL-progressive type groups.

[0264] The statistically significant oligonucleotides obtained were:

SG26, SG31, SG70, SG98, SG177, SG194, SG195, SG208, SG213, SG216, SG272, SG293, SG301, SG309, SG321, SG333, SG343, SG352, SG357, SG366, SG368, SG405, SG426, SG439, SG447, SG452, SG521, SG555, SG556.

[0265] The samples were grouped, which was performed with the hclust function of the stats package in R applying Pearson correlations. The tree obtained is shown in part A of FIG. 4.

[0266] The hierarchical grouping of the 12 samples in accordance with the expression of the 29 statistically significant genes obtained grouped the samples correctly: the tree contains two large branches, of which the right branch contains the 6 stable samples and the left branch contains the 6 progressive samples. [0267] Statistical analysis with normalized data by robust quantiles The list of statistically significant genes was obtained from a Welch's test with the mt.maxT function of the multtest package in R with the values of p without adjusting i.e. without exerting any control over the rate of false positives, with a value of p<0.05, and produced a list of 19 genes with statistically significant differences between the CLL-stable type and CLL-progressive type groups: [0268] SG26, SG31, SG177, SG194, SG195, SG197, SG213, SG216, SG293, SG301, SG309, SG333, SG343, SG357, SG366, SG439, SG452, SG555, SG556.

[0269] The supervised grouping of the 12 samples in accordance with the expression of the 19 statistically significant genes obtained gave rise to the tree which appears in part B of FIG. 4, wherein the samples also appear correctly grouped.

[0270] 18 oligonucleotides common to both lists of statistically significant genes were selected and the average intensity of each one of them in the group of stable samples and in the group of progressive samples was calculated, as well as the variation in average intensity between the stable and progressive groups.

[0271] The values obtained are shown in Table 14.

TABLE-US-00014 TABLE 14 Values corresponding to the intensity of 18 significant oligonucleotides to distinguish between CLL-stable and CLL-progressive Stable CLL Progressive CLL Change group group stable/ Significance Average Average progres- Probe (p data vsn) Intensity SD Intensity SD sive SG177 0.001 14 1.71 21 4.84 0.7 SG366 0.001 18 2.33 14 1.80 1.3 SG309 0.004 20 2.76 15 3.58 1.4 SG26 0.005 97 19.20 70, 13.24 1.4 SG452 0.010 16 2.19 12 3.08 1.3 SG216 0.012 46 14.64 31 7.13 1.5 SG333 0.013 36 7.28 53 16.25 0.7 SG357 0.014 134 6.50 175 38.67 0.8 SG213 0.014 26 5.51 41 17.20 0.6 SG31 0.014 69 32.50 30 10.57 1.8 SG301 0.014 21 5.02 16 3.10 1.4 SG194 0.019 37 9.52 50 9.95 0.7 SG456 0.022 11 2.06 14 2.08 0.8 SG293 0.029 17 1.88 21 3.72 0.8 SG343 0.033 27 7.43 21 1.61 1.3 SG439 0.038 18 2.00 20 1.74 0.9 SG195 0.041 21 3.56 25, 4.60 0.8 SG555 0.049 163 23.55 137 20.69 1.2

[0272] To validate the results obtained with the microarray, 5 of the common statistically significant probes were selected obtained on comparing expression data from stable CLL subjects compared to progressive CLL subjects and the expression was studied with RT-PCR of the genes represented by those probes. The criteria used to select the 5 probes were: hybridization intensity, change of intensity between groups of stable and progressive and value of statistical significance. In this way, 5 probes were selected which represent genes PSMB4, CD23A, LCP1, ABCC5 and POU2F2. The expression of these 5 genes was determined in 11 of the 12 CLL type samples, as there was no total RNA of sample 105. With the expression value of the genes in each sample, the rate of change was determined between the group of stable and progressive and the value of significance of that variation and it was compared with the results obtained with the microarrays.

[0273] The technique used for the validation was RT-PCR or PCR in real time using a LightCycler. This technique is the technique of choice to validate data chips and as with the microarrays, measures mRNA level.

[0274] Primers were designed for each one of the 5 genes whose representative oligonucleotide was selected. The details thereof are shown below in Table 15.

TABLE-US-00015 TABLE 15 Primers and amplification products of the genes selected for their validation by RT-PCR Amplified product Gene Primer sequences (5'-3') SEQ ID NO: size T.sub.m PSMB4 Direct: PSMB4_F SEQ ID NO: 598 95 pb 81.degree. C. TTCTGGGAGATGGACACAGCTATA Inverse: PSMB4_R SEQ ID NO: 599 CCACAAAGGGTTCATCTTCGA CD23A Direct: CD23A_F SEQ ID NO: 600 97 pb 82.degree. C. TGCCCTGAAAAGTGGATCAAT Reverse: CD23A_R SEQ ID NO: 601 CCATGTCGTCACAGGCATACC LCP1 Direct: LCP1_F SEQ ID NO: 602 126 pb 77.degree. C. CCAGGTACCCTTCTCGCTTTT Reverse: LCP1_R SEQ ID NO: 603 CTCCTGGCCCTCATCTTGAA ABCC5 Direct: ABCC5_F SEQ ID NO: 604 119 pb 82.degree. C. CCCTCAAAGTCTGCAACTTTAAGC Reverse: ABCC5_R SEQ ID NO: 605 ACACACCAAACCACACAGCAA POU2F2 Direct: POU2F2_F SEQ ID NO: 606 136 pb 82.degree. C. GAGGACCAGCATCGAGACAAA Reverse: POU2F2_R SEQ ID NO: 607 AACCAGACGCGGATCACTTC

[0275] FIG. 5 shows the distribution of the expression data obtained by RT-PCR (left graphic) and by the microarray (right graphic). Part A corresponds to gene PSMB4, part B to gene CD23A and part C to gene POU2F2.

[0276] Below, in Table 16, the results obtained with the microarray and with RT-PCR are obtained of the change values of the 5 genes selected in thr group of stable samples compared with the group of progressive samples obtained as significance of the change. In 3 of the 5 genes selected (PSMB4, CD23A and POU2F2) the values of change, the direction of the change and the significance values obtained with RT-PCR agree with those obtained with the microarray, for which reason those 3 genes are considered valid, i.e. the results obtained for those 3 genes with the microarray coincide with the results obtained by another techniques which also measures mRNA level.

TABLE-US-00016 TABLE 16 Values of change and significance of the change obtained with the microarray and by RT-PCR Stable/progressive change Significance of the change Probes Genes Array RT-PCR Array RT-PCR SG26 PSBM4 1.3 1.5 0.04 0.15 SG216 CD23A 1.5 3.2 0.04 0.03 SG333 LCP1 0.7 1 0.05 0.97 SG357 ABCC5 0.8 1.3 0.10 0.28 SG366 POU2F2 1.3 2.3 0.01 0.05

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Blood 101:1277, 2003 [0332] Shaffer A L, Rosenwald A, Staudt L M Lymphoid malignancies: the dark side of B-cell differentiation Nat Rev Immunol. 2002; 2:920-32 [0333] Tenen D G, Hromas R, Licht J D, Zhang D E Transcription factors, normal myeloid development, and leucemia. Blood. 1997; 90:489-519 [0334] Tibshirani R, Hastie T, Narasimhan B, Chu G. Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc. Natl. Acad. Sci. 2002; 99:6567-72 [0335] Vardiman J W, Harris N L, Brunning R D The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002; 100:2292-302 [0336] Venables, Smith et al. An Introduction to R, Notes on R: A programming Environment for Data Analysis. 2004 [0337] Weissman I L Stem cells: Units of regeneration and units in evolution. Cell, 2000; 100:157-168. [0338] Westbrook C A. The molecular basis of neoplasia. In Hoffman R Hematology Basic Principles and practice. 4 ed. Churchill Livingstone New York 2005; 941-945 [0339] Zhan F, Hardin J, Kordsmeier B, et al: Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells. Blood 99:1745, 2002

BRIEF DESCRIPTION OF THE FIGURES

[0340] FIG. 1 shows the grouping of samples of cells U937 compared with Jurkat cells in accordance with differences in the gene expression between the samples. Part A corresponds to the non-supervised grouping; part B corresponds to the supervised grouping.

[0341] FIG. 2 shows the grouping of samples of healthy subjects compared with U937 and Jurkat cells in accordance with differences in the gene expression between the samples. Part A corresponds to the non-supervised grouping; part B corresponds to the supervised grouping.

[0342] FIG. 3 shows the grouping of samples of patients with chronic lymphatic leukemia compared with U937 and Jurkat cells in accordance with differences in the gene expression between the samples. Part A corresponds to the non-supervised grouping; part B corresponds to the supervised grouping.

[0343] FIG. 4 shows the grouping of samples of patients with "stable" chronic lymphatic leukemia compared with samples of patients with "progressive" chronic lymphatic leukemia in accordance with differences in gene expression. Part A corresponds to the grouping in accordance with the genes identified as significant after normalization with "vsn" and use of the mt.maxT function in R; part B corresponds to the grouping in accordance with the genes identified as significant after normalization by robust quartiles and use of the mt.maxT function in R.

[0344] FIG. 5 shows the distribution of the expression data obtained by RT-PCR (left-hand graphic) and from the intensity values obtained from the microarray (right-hand graphic) for the PSMB4 genes (part A: upper graphic), CD23A (part B: intermediate graphic) and POU2F2 (part C: lower graphics) in samples of patients with "stable" chronic lymphatic leukemia (bars marked with "E") and in samples of patients with "progressive" chronic lymphatic leukemia (bars marked with "P").

Sequence CWU 1

1

607150DNAArtificial SequenceProbe SG1 designed to hybridize with cRNA of the human gene GABARAP 1tccagtgatt gttttggttt ctgttccctt tctgactgcc caaggggctc 50250DNAArtificial SequenceProbe SG2 designed to hybridize with cRNA of the human gene IGLV6-57 2ttatgatagc acctatcatg tgatattcgg cggagggacc aagctgaccg 50355DNAArtificial SequenceProbe SG3 designed to hybridize with cRNA of the human gene PCD 3gccgtctctt gctccctaat tcatttccca ggaagctgtg atacagggtg aaata 55453DNAArtificial SequenceProbe SG4 designed to hybridize with cRNA of the human gene NCALD 4ccactgaccc tgtctgtatt ttctcggagg ttgtttttct ccttctcctt ccc 53555DNAArtificial SequenceProbe SG5 designed to hybridize with cRNA of the human gene DLAD 5gagtccacac caagccttca gaagtggagg attcatttgt acccagaatt ggcaa 55655DNAArtificial SequenceProbe SG6 designed to hybridize with cRNA of the human gene SOSTDC1 6cgcttggaat ggaatgccag aaatgcatgg cagcagctaa taagtaaagc tgatt 55755DNAArtificial SequenceProbe SG7 designed to hybridize with cRNA of the human gene T1A-2 7ggaaagaccg ttcaccagac ttggctcctc taaacatttg ctgttcaaac atgtt 55855DNAArtificial SequenceProbe SG8 designed to hybridize with cRNA of the human gene PYGB 8ccctgaccac cactgtgccc ctcattgtta ctgccttgtg agataaaaac tgatt 55951DNAArtificial SequenceProbe SG9 designed to hybridize with cRNA of the human gene LIMS1 9atgggcaagc agtggcatgt ggagcatttt gtttgtgcca agtgtgagaa a 511051DNAArtificial SequenceProbe SG10 designed to hybridize with cRNA of the human gene ABL1 10atccaaatct gtcctcgtcc tccagctgtt atctggaaga agcccttcag c 511150DNAArtificial SequenceProbe SG11 designed to hybridize with cRNA of the human gene DRG1 11attgtgaaga agtgaaacct ttcccttttc ccatctgccg gacgaaccac 501250DNAArtificial SequenceProbe SG12 designed to hybridize with cRNA of the human gene BRMS1 12agaagacagc cgaagtcaaa gccacatcct cttgctgatg ttggatgcag 501355DNAArtificial SequenceProbe SG13 designed to hybridize with cRNA of the human gene ABHD1 13gaggacagaa acagctgaca agagtaccat ttggggtctc agttcactct ttcct 551455DNAArtificial SequenceProbe SG14 designed to hybridize with cRNAof the human gene IFRD1 14tgaattcctt cgaaatgtat ttgaacttgg acccccagtg atgcttgatg ctgca 551555DNAArtificial SequenceProbe SG15 designed to hybridize with cRNA of the human gene RPL36A 15cgttgagccc aactgcagat ctaagagaat gctggctatt aaaagatgca agcat 551650DNAArtificial SequenceProbe SG16 designed to hybridize with cRNA of the human gene IGFBP2 16agttctgaca cacgtattta tatttggaaa gagaccagca ccgagctcgg 501750DNAArtificial SequenceProbe SG17 of designed to hybridize with cRNA the human gene NDRG1 17gactttcctt ccctctcctg cttcctcttt tcctgctccc taacctttcg 501855DNAArtificial SequenceProbe SG18 designed to hybridize with cRNA of the human gene FKBP9 18cgtgactcac catgcccagc cacttagttt tttcttattc ccacctttct atccc 551950DNAArtificial SequenceProbe SG19 designed to hybridize with cRNA of the human gene NDP52 19tttttttttt gaaacagtct ctctctgtca cccaggctgg cgtgcaatgg 502055DNAArtificial SequenceProbe SG20 designed to hybridize with cRNA of the human gene FABP5 20ggtgcattgg ttcagcatca ggagtgggat gggaaggaaa gcacaataac aagaa 552155DNAArtificial SequenceProbe SG21 designed to hybridize with cRNA of the human gene FARP1 21acggtttcca gtactaacaa agggaataaa aatacctcac gccacaatcc agcat 552246DNAArtificial SequenceProbe SG22 designed to hybridize with cRNA of the human gene PGF 22ggaagaggag gagagagaag cagagaccca cagactgcca cctgtg 462355DNAArtificial SequenceProbe SG23 designed to hybridize with cRNA of the human gene GDI2 23gcctgagaag gaaatcagac cagctttgga gctcttggaa ccaattgaac agaaa 552455DNAArtificial SequenceProbe SG24 designed to hybridize with cRNA of the human gene TAGLN2 24gagggctgcc taccatggtc tggggcttga ggaagatgag tttgttgatt taaat 552555DNAArtificial SequenceProbe SG25 designed to hybridize with cRNA of the human gene BLVRB 25ggacatgagg agcaaaggaa gggggcaata aatgttgagc caagagcttc aaatt 552650DNAArtificial SequenceProbe SG26 designed to hybridize with cRNA of the human gene PSMB4 26ttacaaccgg tttcaaaccg ccactgtcac cgaaaaaggt gttgaaatag 502750DNAArtificial SequenceProbe SG27 designed to hybridize with cRNA of the human gene TACSTD2 27gaccacatat gcttgtcact gggaaagaag cctgtttcag ctgcctgaac 502850DNAArtificial SequenceProbe SG28 designed to hybridize with cRNA of the human gene TCEB1 28acaaggttcg ctacactaac agctccaccg agattcctga attcccaatt 502955DNAArtificial SequenceProbe SG29 designed to hybridize with cRNA of the human gene EEF1A1 29gagaatgttt tgtggacacg ttggttttct tttttgcgtg tggcagtttt agtta 553055DNAArtificial SequenceProbe SG30 designed to hybridize with cRNA of the human gene H3F3A 30ccgcatacgt ggagaacgtg cttaagaatc cactatgatg ggaaacattt cattc 553155DNAArtificial SequenceProbe SG31 designed to hybridize with cRNA of the human gene ODC1 31gcatttgtag cttgtacaat ggcagaatgg gccaaaagct tagtgttgtg acctg 553255DNAArtificial SequenceProbe SG32 designed to hybridize with cRNA of the human gene XRCC5 32cccagtcacc tctgtcttca gcaccctcat aagtcgtcac taatacacag ttttg 553350DNAArtificial SequenceProbe SG33 designed to hybridize with cRNA of the human gene IGFBP3 33ttcacttctc tgtcttctgt ttctctccca cagtgtcgcc cttccaaagg 503451DNAArtificial SequenceProbe SG34 designed to hybridize with cRNA of the human gene NCL 34aggaggagga ggtgaccaca agccacaagg aaagaagacg aagtttgaat a 513555DNAArtificial SequenceProbe SG35 cRNA designed to hybridize with cRNA of the human gene S100A2 35ctgccatgga tctcttgggc ccaggactgt tgatgccttt gagttttgta ttcaa 553653DNAArtificial SequenceProbe SG36 designed to hybridize with cRNA of the human gene RPL24 36tcagctcccc gagttggtgg aaaacgctaa actggcagat tagattttta aat 533755DNAArtificial SequenceProbe SG37 designed to hybridize with cRNA of the human gene GJA1 37cacccctaag aatggttctg tgtatgtgaa tgagcgggtg gtaattgtgg ctaaa 553850DNAArtificial SequenceProbe SG38 designed to hybridize with cRNA of the human gene GUSB 38aatgtttgga aaacagcccg tttacttgag caagactgat accacctgcg 503955DNAArtificial SequenceProbe SG39 designed to hybridize with cRNA of the human gene HSD17B1 39gttggagacc agccagagca acacagtgag acccccatct ctacaaaaat aaaga 554050DNAArtificial SequenceProbe SG40 designed to hybridize with cRNA of the human gene SFTPB 40ttttcaaaaa atcagcaatt ccccagcgta gtcaagggtg gacactgcac 504150DNAArtificial SequenceProbe SG41 designed to hybridize with cRNA of the human gene RPL23A 41attcggcctg atggagagaa gaaggcatat gttcgactgg ctcctgatta 504255DNAArtificial SequenceProbe SG42 designed to hybridize with cRNA of the human gene CSRP2 42ggctaactcg taggaagaga gcactgtatg gtatcctttt gctttattca ccagc 554355DNAArtificial SequenceProbe SG43 designed to hybridize with cRNA of the human gene CXADR 43tgctgttgtg tgatcaaaca tgtctctgtg tagttccagc aaatcaagct gagct 554450DNAArtificial SequenceProbe SG49 designed to hybridize with cRNA of the human gene EEF1G 44tttggaacca acaatagcag ctccatttct ggagtctggg tcttccgagg 504554DNAArtificial SequenceProbe SG45 designed to hybridize with cRNA of the human gene CKS2 45tgcatgagct gtattcttca cagcaacaga gctcagttaa atgcaactgc aagt 544651DNAArtificial SequenceProbe SG46 designed to hybridize with cRNA of the human gene COL4A6 46attaatggca tatggtccta gacaaaccat ctcctccttg ccggctcccc c 514755DNAArtificial SequenceProbe SG47 designed to hybridize with cRNA of the human gene CRYAB 47gctgtcaccg cagcccccaa gaaatagatg ccctttcttg aattgcattt tttaa 554855DNAArtificial SequenceProbe SG48 designed to hybridize with cRNA of the human gene CYC1 48gctctagctc tgggccctcc ttcagccccc atcatgggaa taaattaatt ttctc 554950DNAArtificial SequenceProbe SG49 designed to hybridize with cRNA of the human gene FNTB 49tcactcctcc ctatcatgta ccgtgaaaac cccctctgat ggcctcaagg 505050DNAArtificial SequenceProbe SG50 designed to hybridize with cRNA of the human gene GOT1 50aaagatcaag ttgtctgaag gagccaaagt gtgaatgtgg gtgtcggctg 505146DNAArtificial SequenceProbe SG51 designed to hybridize with cRNA of the human gene LGALS7 51cttggttcct cccaatgcca gcaggttcca tgtaaacctg ctgtgc 465250DNAArtificial SequenceProbe SG52 designed to hybridize with cRNA of the human gene SERPINB5 52ttgatagctg tcccatctgg tcatgtggtt ggcactagac tggtggcagg 505350DNAArtificial SequenceProbe SG53 designed to hybridize with cRNA of the human gene PSMC5 53agaaaaattg ctgagctcat gccaggagca tcaggggctg aagtgaaggg 505455DNAArtificial SequenceProbe SG54 designed to hybridize with cRNA of the human gene PTN 54ccctgtggca aactgaccaa gcccaaacct caagcagaat ctaagaagaa gaaaa 555555DNAArtificial SequenceProbe SG55 designed to hybridize with cRNA of the human gene RBBP8 55ggcaaggagc agaagacata gacgttgaaa cagaaacaga aggatgaagg acagt 555655DNAArtificial SequenceProbe SG56 designed to hybridize with cRNA of the human gene RGS1 56gcccctcaga actgggaagg ccaggtaact ctagttacac agaaactgtg actaa 555750DNAArtificial SequenceProbe SG57 designed to hybridize with cRNA of the human gene RXRA 57tttcgagtaa tttttaaagc cttgctctgt tgtgtcctgt tgccggctct 505854DNAArtificial SequenceProbe SG58 designed to hybridize with cRNA of the human gene SDHD 58gcttggagtg cttctgaata tacagaagtt ccatttaagg gcaagtttcc ccgt 545950DNAArtificial SequenceProbe SG59 designed to hybridize with cRNA of the human gene SEPW1 59tctcaagggg aagccaagag aggcatcagg atgggtgggt ttctgattgt 506055DNAArtificial SequenceProbe SG60 designed to hybridize with cRNA of the human gene SSBP1 60gccaggcctc agagacgtgg catatcaata tgtgaaaaag gggtctcgaa tttat 556155DNAArtificial SequenceProbe SG61 designed to hybridize with cRNA of the human gene TEGT 61acgaaatcat ttgtttctaa gttgtgttta ttcctggagt gacatgccac cccga 556250DNAArtificial SequenceProbe SG62 designed to hybridize with cRNA of the human gene HIST1H2BN 62tctcgtccaa ggccatgggc atcatgaact ccttcgtcaa tgacatcttc 506355DNAArtificial SequenceProbe SG63 designed to hybridize with cRNA of the human gene BECN1 63ccagccctgg tcagttttga ttcttaaccc catggactcc tttccctttc ttctc 556455DNAArtificial SequenceProbe SG64 designed to hybridize with cRNA of the human gene ANXA7 64gtcaaggacc gtatcagggt aatgtgcttg gtttgcacat gttgttattg cctta 556555DNAArtificial SequenceProbe SG65 designed to hybridize with cRNA of the human gene NDUFA1 65gcgcatctct ggagttgatc gttactatgt gtcaaagggt ttggagaaca ttgat 556650DNAArtificial SequenceProbe SG66 designed to hybridize with cRNA of the human gene ARHGEF2 66ctcaacctct tactgctgtt ctccctttct ccgtccttca tggaagccct 506755DNAArtificial SequenceProbe SG67 designed to hybridize with cRNA of the human gene C5orfl3 67ccattggcct gagtttcttg tgcattactc ctctccctcc ttcgttagaa taggt 556852DNAArtificial SequenceProbe SG68 designed to hybridize with cRNA of the human gene XBP1 68gcatcctggc ttgcctccag ttttaggtcc tttagtttgc ttctgtaagc aa 526950DNAArtificial SequenceProbe SG69 designed to hybridize with cRNA of the human gene G1P2 69agcatccgag caggatcaag ggccggaaat aaaggctgtt gtaagagaat 507053DNAArtificial SequenceProbe SG70 designed to hybridize with cRNA of the human gene GLUD1 70gcccctactc acctgacttt gtatcctctc cttttagagg ctttgcattc tgc 537155DNAArtificial SequenceProbe SG71 designed to hybridize with cRNA of the human gene S100A2 71ctgccatgga tctcttgggc ccaggactgt tgatgccttt gagttttgta ttcaa 557250DNAArtificial SequenceProbe SG72 designed to hybridize with cRNA of the human gene LASP1 72tactaagaat aacaagaagc ccagtggtga ggaaagtgcg ttctcccagc 507350DNAArtificial SequenceProbe SG73 designed to hybridize with cRNA of the human gene TIA-2 73tgtgaaaaat aacagtccac cccaagtcat acactggacc cagtgcctgc 507455DNAArtificial SequenceProbe SG74 designed to hybridize with cRNA of the human gene PGRMC1 74cctgaaccac gaggaaacag tacagtcgct agtcaagtgg tttttaaagt aaagt 557550DNAArtificial SequenceProbe SG75 designed to hybridize with cRNA of the human gene ZFPL1 75caagcctaag acactaagac cccagaccca aagccaagtc caccagagtg 507650DNAArtificial SequenceProbe SG76 designed to hybridize with cRNA of the human gene MAP4K1 76atatggtgat ggtgttgatg gatggctctg tgaagctggt gaccccggag 507755DNAArtificial SequenceProbe SG77 designed to hybridize with cRNA of the human gene STAT1 77gtggcactgc atacaatctg aggcctcctc tctcagtttt tatatagatg gcgag 557854DNAArtificial SequenceProbe SG78 designed to hybridize with cRNA of the human gene HNRPH3 78gctgaattct agccctagat tttggagtaa aaccccttca gcacttgacc gaaa 547953DNAArtificial SequenceProbe SG79 designed to hybridize with cRNA of the human gene TMEM4 79tcaagtttgc gtgtgagagc attgtggagg aatacgagga tgaactcatt gaa 538051DNAArtificial SequenceProbe SG80 designed to hybridize with cRNA of the human gene KIAA0247 80gtttggtctg aatggtgtag ttgctggttc cctagagagg aaaaggtggc a 518155DNAArtificial SequenceProbe SG81 designed to hybridize with cRNA of the human gene RIS1 81gtggcctggt gggcgtttct tcttgtactt atgtggtttt ttggctttta ataca 558253DNAArtificial SequenceProbe SG82 designed to hybridize with cRNA of the human gene ARS2 82tcttcaacaa gcatgcagag aaaattgagg aagtgaaaaa ggaagtcgcg ttt 538350DNAArtificial SequenceProbe SG83 designed to hybridize with cRNA of the human gene CA12 83catccactgg ctgaatgatc agggaggcat agcagtgaga gccataggtc 508455DNAArtificial SequenceProbe SG84 designed to hybridize with cRNA of the human gene EEF1B2 84actgcttttg aggactatgt gcagtccatg gatgtggctg ctttcaacaa gatct 558555DNAArtificial SequenceProbe SG85 designed to hybridize with cRNA of the human gene TRIB2 85gcctgtatat gttttgtgaa atggtcctgt ttttgggtag gtgacacgtg gactc 558655DNAArtificial SequenceProbe SG86 designed to hybridize with cRNA of the human gene FLJ22169 86agcgtccagc tcccctcaac gctatatttt gacactaaaa aagaaggttt ctaaa 558750DNAArtificial SequenceProbe SG87 designed to hybridize with cRNA of the human gene ASNS 87aaagaaggat attactaccg tcaagtcttt gaacgccatt acccaggccg 508855DNAArtificial SequenceProbe SG88 designed to hybridize with cRNA of the human gene WBSCR20C 88ggtgagcaaa agtgttgcct gcagaaataa aatgcagaac gtactctacg ataaa 558951DNAArtificial SequenceProbe SG89 designed to hybridize with cRNA of the human gene AKR1A1 89atcctctgta cccctttaat gacccgtact gagaccacag cttcttggcc t 519055DNAArtificial SequenceProbe SG90 designed to hybridize with cRNA of the human gene SPRR1A 90cgggtgcatt tgaggatgga tttggggagg gatcaagtga accatcccta gtctt 559150DNAArtificial SequenceProbe SG91 designed to hybridize with cRNA of the human gene EFNB1 91attaatgtct taattggctg ttgcctgggg aacaggagag ctgctgcagg 509250DNAArtificial SequenceProbe SG92 designed to hybridize with cRNA of the human gene RPS5 92tcaatgctgc caagggctcc tcgaactcct atgccattaa gaagaaggac 509351DNAArtificial SequenceProbe SG93 designed to hybridize with cRNA of the human gene RPS9 93tgctggattg tctcgttttc ctgccaaata aacaggatca gcgctttaaa a 519455DNAArtificial SequenceProbe SG94 designed to hybridize with cRNA of the human gene RPL17 94acggaaaagg aacagattgt tcctaaacca gaagaggagg ttgcccagaa gaaaa 559555DNAArtificial SequenceProbe SG95 designed to hybridize with cRNA of the human gene ETS2 95cgctgcctca atacccacaa aagaccattc ccagtataca taagcacagg atgtt 559655DNAArtificial SequenceProbe SG96 designed to hybridize with cRNA of the human gene EIF4B 96tccttgcctg ctcctgatgc ttggacccct tttattgatc agagtgctct agaat 559750DNAArtificial SequenceProbe SG97 designed to hybridize with cRNA of the human gene ZYX 97tttgatgtct agcccctccc atttccaacc cctccctagc atcccaggtg 509855DNAArtificial SequenceProbe SG98 designed to hybridize with cRNA of the human gene XPO6 98cggacagtcc tttctccagc ccgacatcca cctttttaaa caaaatctct tctac 559955DNAArtificial SequenceProbe SG99 designed to hybridize with cRNA of the human gene LOC285148 99gtcaatacgt agaggtacgc ttttttcctc aggcttaaac ctttgccact gatat 5510050DNAArtificial SequenceProbe SG100 designed to hybridize with cRNA of the human gene C21orf33 100aataaacgcc ttcccaaaat ggcaacttcc cacagccaca tttcagacct 5010150DNAArtificial SequenceProbe SG101 designed to hybridize with cRNA of the human gene EEF1D 101agtgtcgata tcgcagcttt caacaagatc

tgaagcctga gtgtgtgtac 5010251DNAArtificial SequenceProbe SG102 designed to hybridize with cRNA of the human gene PABPC1 102tactacaagc ccaccaagct aaagaggctg cccagaaagc agttaacagt g 5110355DNAArtificial SequenceProbe SG103 designed to hybridize with cRNA of the human gene RBBP6 103gccagctcag cagaaagtca ggacagcaag aagaagaaga aaaagaagga aaaga 5510450DNAArtificial SequenceProbe SG104 designed to hybridize with cRNA of the human gene HRAS 104tttgaggaca tccaccagta cagggagcag atcaaacggg tgaaggactc 5010550DNAArtificial SequenceProbe SG105 designed to hybridize with cRNA of the human gene GGA3 105tactccaagc ctccgtcaca aaaaaaaaat caccagctgc catagacacg 5010654DNAArtificial SequenceProbe SG106 designed to hybridize with cRNA of the human gene CFL1 106cctgtatttt ttttaacaac atccccattc cccacctggt cctccccctt ccca 5410755DNAArtificial SequenceProbe SG107 designed to hybridize with cRNA of the human gene EIF3S2 107gtcattgcac tccatcctga gccacaagag caaaactccg tctcaaaaaa aaaaa 5510855DNAArtificial SequenceProbe SG108 designed to hybridize with cRNA of the human gene KRT18 108gcagggtacc ctttggggag caggaggcca ataaaaagtt cagagttcaa aaaaa 5510950DNAArtificial SequenceProbe SG109 designed to hybridize with cRNA of the human gene IGFIR 109gaaatggaga ataatccagt cctagcacct ccaagcctga gcaagatgat 5011050DNAArtificial SequenceProbe SG110 designed to hybridize with cRNA of the human gene IL8 110agtgattgag agtggaccac actgcgccaa cacagaaatt attgtaaagc 5011150DNAArtificial SequenceProbe SG111 designed to hybridize with cRNA of the human gene IRF1 111ccggacagca ccagtgatct gtacaacttc caggtgtcac ccatgccctc 5011250DNAArtificial SequenceProbbe SG112 designed to hybridize with cRNA of the human gene IRF2 112tcatcaagaa aacatcggat atcacccagg cccgcgtcaa gagctgttaa 5011350DNAArtificial SequenceProbe SG113 designed to hybridize with cRNA of the human gene LYN 113tatgtgagag atccaacgtc caataaacag caaaggccag ttccagaatc 5011450DNAArtificial SequenceProbe SG114 designed to hybridize with cRNA of the human gene LYZ 114gttgtcaaaa cagagatgtc cgtcagtatg ttcaaggttg tggagtgtaa 5011550DNAArtificial SequenceProbe SG115 designed to hybridize with cRNA of the human gene NFKB1A 115gaggacgagc tgccctatga tgactgtgtg tttggaggcc agcgtctgac 5011650DNAArtificial SequenceProbe SG116 designed to hybridize with cRNA of the human gene MAZ 116ccagccctgg tcttgtcttt tcatccctct tccccacgac agaagaagtt 5011750DNAArtificial SequenceProbe SG117 designed to hybridize with cRNA of the human gene CD79A 117caccaagaac cgaatcatca cagccgaggg gatcatcctc ctgttctgcg 5011850DNAArtificial SequenceProbe SG118 designed to hybridize with cRNA of the human gene MCM3 118gaggaaatgc ctcaagtaca cactccaaag acggcagact cacaggagac 5011950DNAArtificial SequenceProbe SG119 designed to hybridize with cRNA of the human gene MEIS1 119gtttcgtaat ggacggtcag caacatatgg gaattagagc accaggacct 5012050DNAArtificial SequenceProbe SG120 designed to hybridize with cRNA of the human gene PRTN3 120cttcgtgatc tggggatgtg ccacccgcct tttccctgac ttcttcacgc 5012150DNAArtificial SequenceProbe SG121 designed to hybridize with cRNA of the human gene MMP2 121gaaccaaagt ctgaagagcg tgaagtttgg aagcatcaaa tccgactggc 5012250DNAArtificial SequenceProbe SG122 designed to hybridize with cRNA of the human gene MMP7 122gtagcagtct agggattaac ttcctgtatg ctgcaactca tgaacttggc 5012350DNAArtificial SequenceProbe SG123 designed to hybridize with cRNA of the human gene MMP8 123ttaccagagt tgcaagaggc aataaatggc ttaactgtag atatggctga 5012450DNAArtificial SequenceProbe SG124 designed to hybridize with cRNA of the human gene DOK1 124cctggtactg caactggcag tggcatcaaa agccacaact cagccctgta 5012550DNAArtificial SequenceProbe SG125 designed to hybridize with cRNA of the human gene PDGFA 125ccgctgtctg caagaccagg acggtcattt acgagattcc tcggagtcag 5012650DNAArtificial SequenceProbe SG126 designed to hybridize with cRNA of the human gene PRL 126attatctcaa gctcctgaag tgccgaatca tccacaacaa caactgctaa 5012750DNAArtificial SequenceProbe SG127 designed to hybridize with cRNA of the human gene RAF1 127ctattggtga tagtggagtc ccagcactac cttctttgac tatgcgtcgt 5012850DNAArtificial SequenceProbe SG128 designed to hybridize with cRNA of the human gene RARB 128tcagtggatt gacccaaacc gaatggcagc atcggcacac tgctcaatca 5012950DNAArtificial SequenceProbe SG129 designed to hybridize with cRNA of the human gene OPRD1 129acggtgacca agatctgcgt gttcctcttc gccttcgtgg tgcccatcct 5013050DNAArtificial SequenceProbe SG130 designed to hybridize with cRNA of the human gene RET 130caggcaggtg tgagtggagg caaggagatg gcaaagggat caccaggaac 5013150DNAArtificial SequenceProbe SG131 designed to hybridize with cRNA of the human gene SREBF1 131ttggtgcttc tctttgtcta cggtgagcca gtcacacggc cccactcagg 5013250DNAArtificial SequenceProbe SG132 designed to hybridize with cRNA of the human gene TNF 132agccctctgg cccaggcagt cagatcatct tctcgaaccc cgagtgacaa 5013350DNAArtificial SequenceProbe SG133 designed to hybridize with cRNA of the human gene TERF1 133cctgggtgac aggatcatac gtaccccaaa cctcaacatc acacagtata 5013450DNAArtificial SequenceProbe SG134 designed to hybridize with cRNA of the human gene VCAM1 134tctcccctgg accccggatt gctgctcaga ttggagactc agtcatgttg 5013550DNAArtificial SequenceProbe SG135 designed to hybridize with cRNA of the human gene ATP5O 135ccaagtattg aaattggagg ctaagactga tccgtcaatc ttgggtggaa 5013650DNAArtificial SequenceProbe SG136 designed to hybridize with cRNA of the human gene TNFSF5 136caggtgcttc ggtgtttgtc aatgtgactg atccaagcca agtgagccat 5013750DNAArtificial SequenceProbe SG137 designed to hybridize with cRNA of the human gene POLR2C 137gaagaaactg agtgatttac aaactcaatt aagccacgag atccagagtg 5013850DNAArtificial SequenceProbe SG138 designed to hybridize with cRNA of the human gene PLA2G6 138agctcagccc ccaccgatca gcctaaacaa cctagaacta caggatctca 5013950DNAArtificial SequenceProbe SG139 designed to hybridize with cRNA of the human gene CCT6A 139tcttggttga tgagatcatg cgagctggaa tgtcttctct gaaaggttga 5014050DNAArtificial SequenceProbe SG140 designed to hybridize with cRNA of the human gene PDHA1 140ccacagacca tctcatcaca gcctaccggg ctcacggctt tactttcacc 5014150DNAArtificial SequenceProbe SG141 designed to hybridize with cRNA of the human gene LADH 141cggaataaag gatgatgtct tccttagtgt tccttgcatt ttgggacaga 5014250DNAArtificial SequenceProbe SG142 designed to hybridize with cRNA of the human gene SNRPB 142gaactccaaa caagcagaaa gggaagagaa gcgagtcctc ggtctggtgc 5014350DNAArtificial SequenceProbe SG143 designed to hybridize with cRNA of the human gene SNRPB 143tacaaacccg aggaccctct tagggaagaa gccctacatt tgcagtgatt 5014450DNAArtificial SequenceProbe SG144 designed to hybridize with cRNA of the human gene H2AFX 144aggcgccctc gggcggcaag aaggccaccc aggcctccca ggagtactaa 5014550DNAArtificial SequenceProbe SG145 designed to hybridize with cRNA of the human gene MRPL37 145ggctatcctt acccctatcc ccataccctg tacttactgg acaaagccaa 5014650DNAArtificial SequenceProbe SG146 designed to hybridize with cRNA of the human gene UBE2C 146cctgctatca ccccaacgtg gacacccagg gtaacatatg cctggacatc 5014750DNAArtificial SequenceProbe SG147 designed to hybridize with cRNA of the human gene RPS3 147aagaaagcat tcatgggacc actgaagaaa gaccgaattg caaaggaaga 5014850DNAArtificial SequenceProbe SG148 designed to hybridize with cRNA of the human gene ALDH1A1 148actgggagag tacggtttcc atgaatatac agaggtcaaa acagtcacag 5014950DNAArtificial SequenceProbe SG149 designed to hybridize with cRNA of the human gene AF1q 149gcagaccagg agaaaaaccc tgaaggtgat ggcctccttg agtacagcac 5015050DNAArtificial SequenceProbe SG150 designed to hybridize with cRNA of the human gene RUNX1 150ctccctgaac cactccactg cctttaaccc tcagcctcag agtcagatgc 5015150DNAArtificial SequenceProbe SG151 designed to hybridize with cRNA of the human gene MYBL1 151atgggaagac agaagaccaa cttattatga ctgaacaagc aagaagatat 5015250DNAArtificial SequenceProbe SG152 designed to hybridize with cRNA of the human gene ANXA6 152tgagaaatat gacaagtctc tccaccaagc cattgagggt gacacctccg 5015350DNAArtificial SequenceProbe SG153 designed to hybridize with cRNA of the human gene ALK 153gtcattacga ggataccatt ctgaaaagca agaatagcat gaaccagcct 5015450DNAArtificial SequenceProbe SG154 designed to hybridize with cRNA of the human gene MNDA 154gtgtgagaaa ggagataaac ttcgactctt ctgccttcaa ctgagaacag 5015550DNAArtificial SequenceProbe SG155 designed to hybridize with cRNA of the human gene APAF1 155ggtggaacgt tgtcactggg gaatcctcac agaccttcta cacaaatgga 5015650DNAArtificial SequenceProbe SG156 designed to hybridize with cRNA of the human gene BIRC3 156aggcgacact ttcctaattg cttctttgtt ttgggccgga atcttaatat 5015750DNAArtificial SequenceProbe SG157 designed to hybridize with cRNA of the human gene ABCC6 157tgtccttcaa gatccacgca ggagagaagg tgggcatcgt tggcaggacc 5015850DNAArtificial SequenceProbe SG158 designed to hybridize with cRNA of the human gene ATIC 158gaactgggaa tcatcctcgc tcatacgaac cttcggctct tccaccactg 5015950DNAArtificial SequenceProbe SG159 designed to hybridize with cRNA of the human gene ATM 159tgaggaatta gatgaacgtg agcgaaactc tcgtccttct agtaaaaatc 5016050DNAArtificial SequenceProbe SG160 designed to hybridize with cRNA of the human gene BAX 160ttgtcgccct tttctacttt gccagcaaac tggtgctcaa ggccctgtgc 5016150DNAArtificial SequenceProbe SG161 designed to hybridize with cRNA of the human gene CCND1 161cttcctgtcc tactaccgcc tcacacgctt cctctccaga gtgatcaagt 5016250DNAArtificial SequenceProbe SG162 designed to hybridize with cRNA of the human gene BCL2 162ttgctgggac tgtacccaag aattaaacca agacaaagga gcttggcctg 5016350DNAArtificial SequenceProbe SG163 designed to hybridize with cRNA of the human gene BCL3 163tttcctctgg tgaacctgcc tacaccccta taccccatga tgtgccccat 5016450DNAArtificial SequenceProbe SG164 designed to hybridize with cRNA of the human gene BCL6 164tcaataacat cgttaacagg tccatgacgg gctctccccg cagcagcagc 5016550DNAArtificial SequenceProbe SG165 designed to hybridize with cRNA of the human gene BCL7A 165gttgtcgggg gatctggaag gagtgccacc ctctaaaaag atgaaactgg 5016650DNAArtificial SequenceProbe SG166 designed to hybridize with cRNA of the human gene BCL7b 166caaggaagaa ccagttccac tagagacaca ggtcgttgag gaagaggaag 5016750DNAArtificial SequenceProbe SG167 designed to hybridize with cRNA of the human gene BCL10 167gcacgacgcc ctttttttct actaattctt ctctgaattt gcctgttcta 5016850DNAArtificial SequenceProbe SG168 designed to hybridize with cRNA of the human gene BCL2L1 168gtagacaagg agatgcaggt attggtgagt cggatcgcag cttggatggc 5016950DNAArtificial SequenceProbe SG169 designed to hybridize with cRNA of the human gene BCR 169gcagggagtt cagcttgaag aggatgccgt cccgaaaaca gacaggggtc 5017050DNAArtificial SequenceProbe SG170 designed to hybridize with cRNA of the human gene BCR 170aatgtctgag gaagcatcgg agactgggtc ccgccatgcc tgtgtcatct 5017150DNAArtificial SequenceProbe SG171 designed to hybridize with cRNA of the human gene OLIG2 171caactacatc ctcatgctca ccaactcgct ggaggagatg aagcgactgg 5017250DNAArtificial SequenceProbe SG172 designed to hybridize with cRNA of the human gene BIK 172caccacactt aaggagaaca taatgaggtt ctggagatcc ccgaaccccg 5017350DNAArtificial SequenceProbe SG173 designed to hybridize with cRNA of the human gene BCL2LAA 173cagagccaca aggtaatcct gaaggcaatc acggaggtga aggggacagc 5017450DNAArtificial SequenceProbe SG174 designed to hybridize with cRNA of the human gene BMI1 174caatagacct cgaaaatcat cagtaaatgg gtcatcagca acttcttctg 5017550DNAArtificial SequenceProbe SG175 designed to hybridize with cRNA of the human gene BLMH 175ctaggcccca gcacaagtac aacaaacttt acacagtgga atacttaagc 5017650DNAArtificial SequenceProbe SG176 designed to hybridize with cRNA of the human gene BLR1 176ttctgggaac tggacagatt ggacaactat aacgacacct ccctggtgga 5017750DNAArtificial SequenceProbe SG177 designed to hybridize with cRNA of the human gene IBSP 177cgtcaatgaa tacgacaatg gatatgaaat ctatgaaagt gagaacgggg 5017850DNAArtificial SequenceProbe SG178 designed to hybridize with cRNA of the human gene BTG1 178gtagcactca aaacagcacc aacgtgcaaa tggtagacag ccgaatcagc 5017950DNAArtificial SequenceProbe SG179 designed to hybridize with cRNA of the human gene BUB1 179gaaatacaat caacggagaa agcatgagca atgggtaaat gaagacagac 5018050DNAArtificial SequenceProbe SG180 designed to hybridize with cRNA of the human gene ABL1 180gcaagctcct cagttcggtg aaggaaatca gtgacatagt gcagaggtag 5018150DNAArtificial SequenceProbe SG171 designed to hybridize with cRNA of the human gene CASP1 181ggactctcag cagatcaaac atctggaaat taccttaata tgcaagactc 5018250DNAArtificial SequenceProbe SG182 designed to hybridize with cRNA of the human gene CASP3 182cctggttatt attcttggcg aaattcaaag gatggctcct ggttcatcca 5018350DNAArtificial SequenceProbe SG183 designed to hybridize with cRNA of the human gene CASP4 183aaatatcccc caataaaaaa gctcatccga atatggaggc tggaccacct 5018450DNAArtificial SequenceProbe SG184 designed to hybridize with cRNA of the human gene CASP5 184ctggacaaac atctatccag accctagtac ctaatacgga tcaaaagtcg 5018550DNAArtificial SequenceProbe SG185 designed to hybridize with cRNA of the human gene CASP6 185ggttccctgt tttgcctcaa tgctaactaa aaagctgcat ttctttccaa 5018650DNAArtificial SequenceProbe SG186 designed to hybridize with cRNA of the human gene CASP7 186tcccctgtgt ggtctccatg ctcaccaagg aactctactt cagtcaatag 5018750DNAArtificial SequenceProbe SG187 designed to hybridize with cRNA of the human gene CASP8 187gcagcagcct tgaaggaagt cctgatgaat tttcaaatga ctttggacaa 5018850DNAArtificial SequenceProbe SG188 designed to hybridize with cRNA of the human gene CASP9 188gtccctcctg cttagggtcg ctaatgctgt ttcggtgaaa gggatttata 5018950DNAArtificial SequenceProbe SG189 designed to hybridize with cRNA of the human gene CBFB 189gctcccatga ttctgaatgg agtctgtgtt atctggaaag gctggattga 5019050DNAArtificial SequenceProbe S90 designed to hybridize with cRNA of the human gene CALD1 190caaaagaggg aggagatgcg actcgaagca gaaagaatcg cctaccagag 5019150DNAArtificial SequenceProbe SG191 designed to hybridize with cRNA of the human gene CAST 191agcaggcatc agatacagga agtaacgatg ctcacaataa aaaagcagtt 5019250DNAArtificial SequenceProbe SG192 designed to hybridize with cRNA of the human gene CDC25A 192caggggagaa gagcaagagg gagatgtaca gtcgtctgaa gaagctctga 5019350DNAArtificial SequenceProbe SG193 designed to hybridize with cRNA of the human gene CDC25B 193ttccctcagc acccgaactt ctgtgaaccc caggactacc ggcccatgaa 5019450DNAArtificial SequenceProbe SG194 designed to hybridize with cRNA of the human gene CD2 194aaattccagc ttcaacccct cagaatccag caacttccca acatcctcct 5019550DNAArtificial SequenceProbe SG195 designed to hybridize with cRNA of the human gene CD3E 195aagatgcgaa cttttatctc tacctgaggg caagagtgtg tgagaactgc 5019650DNAArtificial SequenceProbe SG196 designed to hybridize with cRNA of the human gene CD4 196ctccaaccag ataaagattc tgggaaatca gggctccttc ttaactaaag 5019750DNAArtificial SequenceProbe SG197 designed to hybridize with cRNA of the human gene CD5 197ggaaaatatg ccctccccgt aatggtgaac caccagcacc tacccaccac 5019850DNAArtificial SequenceProbe SG198 designed to hybridize with cRNA of the human gene CD6 198tcatctaaag acaccttcct ttccactggc tgtcaagcca cagggcacca 5019950DNAArtificial SequenceProbe SG199 designed to hybridize with cRNA of the human gene CD7 199gtgctcgtgg cgggataaga attcggcggc atgtgtggtg tacgaggaca 5020050DNAArtificial SequenceProbe SG200 designed to hybridize with cRNA of the human gene CD8 200ttcattctca atctcacaag cgtgaagccg gaagacagtg gcatctactt 5020150DNAArtificial SequenceProbe SG201 designed to hybridize with cRNA of the human gene CD9 201gtgaagtcct gtcctgatgc catcaaagag gtcttcgaca ataaattcca 5020250DNAArtificial SequenceProbe SG202

designed to hybridize with cRNA of the human gene MME 202tcagaagcct ttcactgccg caagaattca tacatgaatc cagaaaagaa 5020350DNAArtificial SequenceProbe SG203 designed to hybridize with cRNA of the human gene ITGAL 203tgcctgaagc ccctccatga gaaggactct gagagtggtg gtggcaagga 5020450DNAArtificial SequenceProbe SG204 Designed to hybridize with cRNA of the human gene ITGAM 204tttgtgaggt cccagacgga gaccaaagtg gagccgttcg aggtccccaa 5020550DNAArtificial SequenceProbe SG205 Designed to hybridize with cRNA of the human gene ITGAX 205aggaggcaaa tggacaaatt gccccagaaa acgggacaca gacccccagc 5020650DNAArtificial SequenceProbe SG206 Designed to hybridize with cRNA of the human gene ANPEP 206agccctggag aagacgaaag ccaacatcaa gtgggtgaag gagaacaagg 5020750DNAArtificial SequenceProbe SG207 Designed to hybridize with cRNA of the human gene CD14 207tggataacct gacactggac gggaatccct tcctggtccc tggaactgcc 5020850DNAArtificial SequenceProbe SG208 Designed to hybridize with cRNA of the human gene SELE 208aattgggctc ctgcacacag tggcccgcta caagttctac ctggctttcg 5020950DNAArtificial SequenceProbe SG209 Designed to hybridize with cRNA of the human gene FCGR3A 209gtgaagacaa acattcgaag ctcaacaaga gactggaagg accataaatt 5021050DNAArtificial SequenceProbe SG210 Designed to hybridize with cRNA of the human gene FCGR3B 210gcttggtgat ggtactcctt tttgcagtgg acacaggact atatttctct 5021150DNAArtificial SequenceProbe SG211 Designed to hybridize with cRNA of the human gene ITGB2 211gataatcccc ttttcaagag cgccaccacg acggtcatga accccaagtt 5021250DNAArtificial SequenceProbe SG212 Designed to hybridize with cRNA of the human gene CD19 212actccattcg gggccagcct ggacccaatc atgaggaaga tgcagactct 5021350DNAArtificial SequenceProbe SG213 Designed to hybridize with cRNA of the human gene MS4A1 213ctccccaaga tcaggaatcc tcaccaatag aaaatgacag ctctccttaa 5021450DNAArtificial SequenceProbe SG214 Designed to hybridize with cRNA of the human gene CR2 214catttagaag cacgagaagt atattctgtt gatccataca acccagccag 5021550DNAArtificial SequenceProbe SG215 Designed to hybridize with cRNA of the human gene CD22 215acgtcattcc agattttcca gaagatgagg ggattcatta ctcagagctg 5021650DNAArtificial SequenceProbe SG216 Designed to hybridize with cRNA of the human gene FCER2 216actccgggag gaggtgacaa agctaaggat ggagttgcag gtgtccagcg 5021750DNAArtificial SequenceProbe SG217 Designed to hybridize with cRNA of the human gene CD24 217cagccagtct cttcgtggtc tcactctctc ttctgcatct ctactcttaa 5021850DNAArtificial SequenceProbe SG218 Designed to hybridize with cRNA of the human gene IL2RA 218ctgctgagag cgtctgcaaa atgacccacg ggaagacaag gtggacccag 5021950DNAArtificial SequenceProbe SG219 Designed to hybridize with cRNA of the human gene DPP4 219gacaaccttg accattacag aaattcaaca gtcatgagca gagctgaaaa 5022050DNAArtificial SequenceProbe SG220 Designed to hybridize with cRNA of the human gene ITGB1 220gagaaaatga atgccaaatg ggacacgcaa gaaaatccga tttacaagag 5022150DNAArtificial SequenceProbe SG221 Designed to hybridize with cRNA of the human gene TNFRSF8 221agacggtcac caagccccag gatatggctg agaaggacac cacctttgag 5022250DNAArtificial SequenceProbe SG222 Designed to hybridize with cRNA of the human gene CD33 222ttacatggcc ccactgaaac ctcaagctgt tcaggtgccg cccctactgt 5022350DNAArtificial SequenceProbe SG223 Designed to hybridize with cRNA of the human gene CD34 223cctgctggct gtcttgggca tcactggcta tttcctgatg aatcgccgca 5022450DNAArtificial SequenceProbe SG224 Designed to hybridize with cRNA of the human gene CD36 224ggcctttgcc tctccagttg aaaacccaga caactattgt ttctgcacag 5022550DNAArtificial SequenceProbe SG225 Designed to hybridize with cRNA of the human gene CD38 225agtgtggaag tccataattt gcaaccagag aaggttcaga cactagaggc 5022650DNAArtificial SequenceProbe SG226 Designed to hybridize with cRNA of the human gene TNFRSF5 226acccaggagg atggcaaaga gagtcgcatc tcagtgcagg agagacagtg 5022750DNAArtificial SequenceProbe SG227 Designed to hybridize with cRNA of the human gene SPN 227acccaggagg atggcaaaga gagtcgcatc tcagtgcagg agagacagtg 5022850DNAArtificial SequenceProbe SG228 Designed to hybridize with cRNA of the human gene CD44 228gagctgtgga ggacagaaag ccaagtggac tcaacggaga ggccagcaag 5022950DNAArtificial SequenceProbe SG229 Designed to hybridize with cRNA of the human gene CD44v6 229ctgggattgg ttttcatggt tgtttctacc atcagagtca aagaatcatc 5023050DNAArtificial SequenceProbe SG230 Designed to hybridize with cRNA of the human gene PTPRCCD 230aacattctgt caatggtcct gcaagtccag ccttaaatca aggttcatag 5023150DNAArtificial SequenceProbe SG231 Designed to hybridize with cRNA of the human gene CD47 231tcaggtgata gcctatatcc tcgctgtggt tggactgagt ctctgtattg 5023250DNAArtificial SequenceProbe SG232 Designed to hybridize with cRNA of the human gene ITGA2 232agccgaagta ccaacaggag ttataatagg aagtataatt gctggaatcc 5023350DNAArtificial SequenceProbe SG233 Designed to hybridize with cRNA of the human gene ITGA3 233ctaagaggca gaaggcggag atgaagagcc agccgtcaga gacagagagg 5023450DNAArtificial SequenceProbe SG234 Designed to hybridize with cRNA of the human gene ITGA4 234cttggactta ttgtacttct gttgatctca tatgttatgt ggaaggctgg 5023550DNAArtificial SequenceProbe SG235 Designed to hybridize with cRNA of the human gene ITGA5 235tcaactgcac caccaatcac cccattaacc caaagggcct ggagttggat 5023650DNAArtificial SequenceProbe SG236 Designed to hybridize with cRNA of the human gene ICAM3 236ctatgcagcc gacagaagca atgggggaag aaccgtccag agctgagtga 5023750DNAArtificial SequenceProbe SG237 Designed to hybridize with cRNA of the human gene CDW52 237ccctcagcat ccagcagcat gagcggaggc attttccttt tcttcgtggc 5023850DNAArtificial SequenceProbe SG238 Designed to hybridize with cRNA of the human gene ICAM1 238gaacaaccgg aaggtgtatg aactgagcaa tgtgcaagaa gatagccaac 5023950DNAArtificial SequenceProbe SG239 Designed to hybridize with cRNA of the human gene NCAM1 239gaggtgaccc cagactctga gaatgatttt gggaactaca actgtactgc 5024050DNAArtificial SequenceProbe SG240 Designed to hybridize with cRNA of the human gene CD58 240catcaatcat tttgacaacc tgtatcccaa gcagcggtca ttcaagacac 5024150DNAArtificial SequenceProbe SG241 Designed to hybridize with cRNA of the human gene CD59 241cgaacagctt gaaaatggtg ggacatcctt atcagagaaa acagttcttc 5024250DNAArtificial SequenceProbe SG242 Designed to hybridize with cRNA of the human gene SELL 242taggaacata tggagttttt acaaacgctg catttgaccc gagtccttaa 5024350DNAArtificial SequenceProbe SG243 Designed to hybridize with cRNA of the human gene CD79B 243gccacctatg aggacatagt gacgctgcgg acaggggaag tgaagtggtc 5024450DNAArtificial SequenceProbe SG244 Designed to hybridize with cRNA of the human gene CD81 244cttcaaggag gactgccacc agaagatcga tgacctcttc tccgggaagc 5024550DNAArtificial SequenceProbe SG245 Designed to hybridize with cRNA of the human gene KAI1 245cctgaggtca cctacccctg ttcctgcgaa gtcaaggggg aagaggacaa 5024650DNAArtificial SequenceProbe SG246 Designed to hybridize with cRNA of the human gene CD83 246caaataagca tttagggcta gtgactcctc acaagacaga actggtatga 5024750DNAArtificial SequenceProbe SG247 Designed to hybridize with cRNA of the human gene CD86 247caactcttat aaatgtggaa ccaacacaat ggagagggaa gagagtgaac 5024850DNAArtificial SequenceProbe SG248 Designed to hybridize with cRNA of the human gene TNFRSF6 248cttccaaatg cagaagatgt agattgtgtg atgaaggaca tgatgtgaac 5024950DNAArtificial SequenceProbe SG249 Designed to hybridize with cRNA of the human gene TNFSF6 249tgaggaactc taagtatccc caggatctgg tgatgatgga ggggaagatg 5025050DNAArtificial SequenceProbe SG250 Designed to hybridize with cRNA of the human gene SLC7A5 250tgacatccca ggggctgtaa gtgccaacat gactgtgaag ggccagagtg 5025150DNAArtificial SequenceProbe SG251 Designed to hybridize with cRNA of the human gene SDC1 251aaacaagcca acggcggggc ctaccagaag cccaccaaac aggaggaatt 5025250DNAArtificial SequenceProbe SG252 Designed to hybridize with cRNA of the human gene CDK4 252ctggaaatgc tgacttttaa cccacacaag cgaatctctg cctttcgagc 5025350DNAArtificial SequenceProbe SG253 Designed to hybridize with cRNA of the human gene STAT3 253agggcagttt gagtccctca cctttgacat ggagttgacc tcggagtgcg 5025450DNAArtificial SequenceProbe SG254 Designed to hybridize with cRNA of the human gene FGR 254gactatgagg ctcgaactga ggatgacctc accttcacca agggcgagaa 5025550DNAArtificial SequenceProbe SG255 Designed to hybridize with cRNA of the human gene FOS 255gagcgcagag cattggcagg aggggcaagg tggaacagtt atctccagaa 5025650DNAArtificial SequenceProbe SG256 Designed to hybridize with cRNA of the human gene CCNE1 256tgtaccaagt ggagcaggtg gttgcgggca agcgttgtgc agagcccata 5025750DNAArtificial SequenceProbe SG257 Designed to hybridize with cRNA of the human gene CDA 257ccgctatcca gaaggccgtc tcagaagggt acaaggattt cagggcaatt 5025850DNAArtificial SequenceProbe SG258 Designed to hybridize with cRNA of the human gene MAFB 258gcaaggagga ggtgatccgg ctgaagcaga agaggcggac cctgaaaaac 5025950DNAArtificial SequenceProbe SG259 Designed to hybridize with cRNA of the human gene MPL 259tgctgtacca cccacattgc caaccattcc tacctaccac taagctattg 5026050DNAArtificial SequenceProbe SG260 Designed to hybridize with cRNA of the human gene MYC 260gttgcggaaa cgacgagaac agttgaaaca caaacttgaa cagctacgga 5026150DNAArtificial SequenceProbe SG261 Designed to hybridize with cRNA of the human gene MYB 261agctaaaagg acagcaggtg ctaccagtaa gactgtcatc atgtgcttga 5026250DNAArtificial SequenceProbe SG262 Designed to hybridize with cRNA of the human gene CKMT1 262gctggtgcag atggtggtgg acggagtgaa gctgctcatc gagatggaac 5026350DNAArtificial SequenceProbe SG263 Designed to hybridize with cRNA of the human gene CREBBP 263cacgtctcac cccagactgg ttccccccac cccggactcg cagtcaccat 5026450DNAArtificial SequenceProbe SG264 Designed to hybridize with cRNA of the human gene CTGF 264catcaagacc tgtgcctgcc attacaactg tcccggagac aatgacatct 5026550DNAArtificial SequenceProbe SG265 Designed to hybridize with cRNA of the human gene CXCR3 265agctttgacc gctacctgaa catagttcat gccacccagc tctaccgccg 5026650DNAArtificial SequenceProbe SG266 Designed to hybridize with cRNA of the human gene CXCR4 266attcatctgt ttccactgag tctgagtctt caagttttca ctccagctaa 5026750DNAArtificial SequenceProbe SG267 Designed to hybridize with cRNA of the human gene CCNA1 267gcaatcatgt accctggatc ttttattggg ggctggggag aagagtatct 5026850DNAArtificial SequenceProbe SG268 Designed to hybridize with cRNA of the human gene CCNB1 268ggacttacaa agcacatgac tgtcaagaac aagtatgcca catcgaagca 5026950DNAArtificial SequenceProbe SG269 Designed to hybridize with cRNA of the human gene CCMD2 269aactggacca agccagcacc cctacagacg tgcgggatat cgacctgtga 5027050DNAArtificial SequenceProbe SG270 Designed to hybridize with cRNA of the human gene CYP1A1 270accaagaact gcttagccta gtcaacctga ataataattt cggggaggtg 5027150DNAArtificial SequenceProbe SG271 Designed to hybridize with cRNA of the human gene CYP2A6 271gcgcatgatg ctaggaatct tccagttcac gtcaacctcc acggggcagc 5027250DNAArtificial SequenceProbe SG272 Designed to hybridize with cRNA of the human gene DAD- 272cggtttgcct gagaatacag atcaacccac agaacaaagc ggatttccaa 5027350DNAArtificial SequenceProbe SG273 Designed to hybridize with cRNA of the human gene TNFRSF10C 273tcatgcacca tcgtagggat catagttcta attgtgcttc tgattgtgtt 5027450DNAArtificial SequenceProbe SG274 Designed to hybridize with cRNA of the human gene DEK 274acagaaagct acttctaaaa gtaaaaaatc tgtgaaaagt gccaatgtta 5027550DNAArtificial SequenceProbe SG275 Designed to hybridize with cRNA of the human gene DCK 275gctggctcct gcataggaca ctgaaaacca acttcgatta tcttcaagag 5027650DNAArtificial SequenceProbe SG276 Designed to hybridize with cRNA of the human gene DHFR 276ccaggtgttc tctctgatgt ccaggaggag aaaggcatta agtacaaatt 5027750DNAArtificial SequenceDesigned to hybridize with cRNA of the human gene TCF3 277tcaggtgtgg ttggagaccc ccagatggtg ctttcagctc cccacccagg 5027850DNAArtificial SequenceProbe SG278 Designed to hybridize with cRNA of the human gene E2F1 278tcagagacct cttcgactgt gactttgggg acctcacccc cctggatttc 5027950DNAArtificial SequenceProbe SG279 Designed to hybridize with cRNA of the human gene TCF3 279tgccagatgc acctcaagtc ggacaaagcg cagaccaagc tgctcatcct 5028050DNAArtificial SequenceProbe SG280 Designed to hybridize with cRNA of the human gene EB-1 280tactttgatg atattccccg atcaaaactg gagaggcaga tggctcagac 5028150DNAArtificial SequenceProbe SG281 Designed to hybridize with cRNA of the human gene CCR7 281gccttcatcg gcgtcaagtt ccgcaacgat ctcttcaagc tcttcaagga 5028250DNAArtificial SequenceProbe SG282 Designed to hybridize with cRNA of the human gene EBI2 282gtcagtgtat cgatttctag tgctgtgaag tcagcccctg aagaaaattc 5028350DNAArtificial SequenceProbe SG283 Designed to hybridize with cRNA of the human gene MUC-1 283tacctcctct cacctcctcc aatcacagca cttctcccca gttgtctact 5028450DNAArtificial SequenceProbe SG284 Designed to hybridize with cRNA of the human gene EphA3 284atgtgggcat tcagctccga cggcccttgt tccagaaggt aaccacggtg 5028550DNAArtificial SequenceProbe SG285 Designed to hybridize with cRNA of the human gene EPOR 285tcagaagcat cctcctgctc atctgctttg gctaccttcc agcataacta 5028650DNAArtificial SequenceProbe SG286 Designed to hybridize with cRNA of the human gene ERCC1 286aaacggacag tcagaccctc ctgaccacat ttggatctct ggaacagctc 5028750DNAArtificial SequenceProbe SG287 Designed to hybridize with cRNA of the human gene ERCC2 287tcaggggcaa gacggactac ggcctcatgg tctttgccga caagcggttt 5028850DNAArtificial SequenceProbe SG288 Designed to hybridize with cRNA of the human gene ERCC3 288cggcgctttg gcaccatgag ttctatgtct ggggccgacg acactgtgta 5028950DNAArtificial SequenceProbe SG289 Designed to hybridize with cRNA of the human gene ERCC5 289tagtgatgac gatggaggga aagagaagat ggtcctcgtg accgccagat 5029050DNAArtificial SequenceProbe SG290 Designed to hybridize with cRNA of the human gene ERCC6 290tgcactttcc atagaacttc tggtggtgaa ggaatttgga aactcaagcc 5029150DNAArtificial SequenceProbe SG291 Designed to hybridize with cRNA of the human gene CUZD1 291cacagtgagg cattttgtaa atcaacgggc agactacaaa taccagaagc 5029250DNAArtificial SequenceProbe SG292 Designed to hybridize with cRNA of the human gene ETV6 292aatcatgagt ggccgaacag accgtctgga gcacctagag tcccaggagc 5029350DNAArtificial SequenceProbe SG293 Designed to hybridize with cRNA of the human gene EIF4E 293attatggaat acaaaactca caccgacagc atcaaaatgc caggcaggct 5029450DNAArtificial SequenceProbe SG294 Designed to hybridize with cRNA of the human gene EIF5A 294ccttggcaag gagattgagc agaagtacga ctgtggagaa gagatcctga 5029550DNAArtificial SequenceProbe SG295 Designed to hybridize with cRNA of the human gene EZH2 295tccacggcag ccttgtgaca gttcgtgccc ttgtgtgata gcacaaaatt 5029650DNAArtificial SequenceProbe SG296 Designed to hybridize with cRNA of the human gene FADD 296atgtccccga tgtcatggaa ctcagacgca tctacctccg aagcgtcctg 5029750DNAArtificial SequenceProbe SG297 Designed to hybridize with cRNA of the human gene PTK2 297gcacccaccg agagattgag atggcacaga agctattgaa ctctgacctg 5029850DNAArtificial SequenceProbe SG298 Designed to hybridize with cRNA of the human gene FAT 298ttgtagagaa ccccatgccc cttacccgcc agggtatcaa agacacttcg 5029950DNAArtificial SequenceProbe SG299 Designed to hybridize with cRNA of the human gene FGFR1 299ttcttctggt tcggccatca cggctctcct ccagtgggac tcccatgcta 5030050DNAArtificial SequenceProbe SG300 Designed to hybridize with cRNA of the human gene FGFR3 300aggagctaga ggttctctcc ttgcacaacg tcacctttga ggacgccggg 5030150DNAArtificial SequenceProbe SG301 Designed to hybridize with cRNA of the human gene FHIT 301tcctgcctct tggagatcag aggaggaaat ggcagcagaa gccgcagctc 5030250DNAArtificial SequenceProbe SG302 Designed to hybridize with cRNA of the human gene FLT3 302tggagcgcgt gaacacggag atacactttg

tcaccaaatg tgcctttcag 5030350DNAArtificial SequenceProbe SG303 Designed to hybridize with cRNA of the human gene GRIA3 303gcgatacttg attgactgcg aagtcgaaag gattaacaca attttggaac 5030450DNAArtificial SequenceProbe SG304 Designed to hybridize with cRNA of the human gene FUS 304gggacagccc atgattaatt tgtacacaga cagggaaact ggcaagctga 5030550DNAArtificial SequenceProbe SG305 Designed to hybridize with cRNA of the human gene EIF4E 305cccacgcaga cacagctact aagagcggct ccaccactaa aaataggttt 5030650DNAArtificial SequenceProbe SG306 Designed to hybridize with cRNA of the human gene SIAT4A 306agactttgag tctaacgtga cggccacctt ggcctccatc aataaaatcc 5030750DNAArtificial SequenceProbe SG307 Designed to hybridize with cRNA of the human gene CSF3 307gcttcctgga ggtgtcgtac cgcgttctac gccaccttgc ccagccctga 5030850DNAArtificial SequenceProbe SG308 Designed to hybridize with cRNA of the human gene CSF2 308ccctccaacc ccggaaactt cctgtgcaac ccagattatc acctttgaaa 5030950DNAArtificial SequenceProbe SG309 Designed to hybridize with cRNA of the human gene NR3C1 309cagccagaac tggcagcggt tttatcaact gacaaaactc ttggattcta 5031050DNAArtificial SequenceProbe SG310 Designed to hybridize with cRNA of the human gene GSTT1 310ataaggtgat gttccctgtg ttcctgggtg ggccagtatc tccccagaca 5031150DNAArtificial SequenceProbe SG311 Designed to hybridize with cRNA of the human gene GZMA 311ggcctggtgt ctatattctt ctctcaaaga aacacctcaa ctggataatt 5031250DNAArtificial SequenceProbe SG312 Designed to hybridize with cRNA of the human gene DNAJA1 312agatcttctg ccatctagac cggaagttcc taacataatt ggagaaacag 5031350DNAArtificial SequenceProbe SG313 Designed to hybridize with cRNA of the human gene HLF 313gatcctgaca ccatccaggt cccagtgggt tatgagccag acccagcaga 5031450DNAArtificial SequenceProbe SG314 Designed to hybridize with cRNA of the human gene BST2 314agaagagaaa accaggtctt aagcgtgaga atcgcggaca agaagtacta 5031550DNAArtificial SequenceProbe SG315 Designed to hybridize with cRNA of the human gene HOXA9 315ggggtgactg tcccacgctt gacactcaca ctttgtccct gactgactat 5031650DNAArtificial SequenceProbe SG316 Designed to hybridize with cRNA of the human gene TLX1 316gacaggttca caggtcaccc ctatcagaac cggacgcccc ccaagaagaa 5031750DNAArtificial SequenceProbe SG317 Designed to hybridize with cRNA of the human gene UHRF1 317cgctacgatg gcatctacaa ggttgtgaaa tactggcccg agaaggggaa 5031850DNAArtificial SequenceProbe SG318 Designed to hybridize with cRNA of the human gene IER3 318aaaaggcttc tctttctgct gctcaccatc gtcttctgcc agatcctgat 5031950DNAArtificial SequenceProbe SG319 Designed to hybridize with cRNA of the human gene IL1B 319cagaccttcc aggagaatga cctgagcacc ttctttccct tcatctttga 5032050DNAArtificial SequenceProbe SG320 Designed to hybridize with cRNA of the human gene IL2 320agcaaccatt gtagaatttc tgaacagatg gattaccttt tgtcaaagca 5032150DNAArtificial SequenceProbe SG321 Designed to hybridize with cRNA of the human gene IL3 321gcacccacgc gacatccaat ccatatcaag gacggtgact ggaatgaatt 5032250DNAArtificial SequenceProbe SG322 Designed to hybridize with cRNA of the human gene IL6 322gaacaagcca gagctgtcca gatgagtaca aaagtcctga tccagttcct 5032350DNAArtificial SequenceProbe SG323 Designed to hybridize with cRNA of the human gene IL6R 323cacggagccc ttatgacatc agcaatacag actacttctt ccccagatag 5032450DNAArtificial SequenceProbe SG324 Designed to hybridize with cRNA of the human gene IL10 324ccaagagaaa ggcatctaca aagccatgag tgagtttgac atcttcatca 5032550DNAArtificial SequenceProbe SG325 Designed to hybridize with cRNA of the human gene IL15 325atacggaaag tgatgttcac cccagttgca aagtaacagc aatgaagtgc 5032650DNAArtificial SequenceProbe SG326 Designed to hybridize with cRNA of the human gene IRF4 326atccagaaga ttaccacaga tctatccgcc attcctctat tcaagaatga 5032750DNAArtificial SequenceProbe SG327 Designed to hybridize with cRNA of the human gene JAK1 327aacgcctgcc gtgcccacct aactgtccag atgaggttta tcagcttatg 5032850DNAArtificial SequenceProbe SG328 Designed to hybridize with cRNA of the human gene JAK2 328aatcaacgcc cctcctttag ggatctagct cttcgagtgg atcaaataag 5032950DNAArtificial SequenceProbe SG329 Designed to hybridize with cRNA of the human gene MKI67 329tgtgtcaaga aaataacaac cagaagtcat agggacagtg aagatatttg 5033050DNAArtificial SequenceProbe SG330 Designed to hybridize with cRNA of the human gene XRCC5 330tgggaaattg ttgtccagga tggaattact ctgatcacca aagaggaagc 5033150DNAArtificial SequenceProbe SG331 Designed to hybridize with cRNA of the human gene LAG3 331agcaagggat tcaccctcgc caggctcaga cgcaagatag aggagctgga 5033250DNAArtificial SequenceProbe SG332 Designed to hybridize with cRNA of the human gene LCK 332cccttcaggc atcaagttga ccatcaacaa actcctggac atggcagccc 5033350DNAArtificial SequenceProbe SG333 Designed to hybridize with cRNA of the human gene LCP1 333tttcaaggac ccgaagatta gtacaagtct gcctgttctg gacctcatcg 5033450DNAArtificial SequenceProbe SG334 Designed to hybridize with cRNA of the human gene LEPR 334agaattgttc ctgggcacaa ggacttaatt ttcagaagag aacggacatt 5033550DNAArtificial SequenceProbe SG335 Designed to hybridize with cRNA of the human gene LMO2 335tgtgcgaaca ggacatctac gagtggacta agatcaatgg gatgatatag 5033650DNAArtificial SequenceProbe SG336 Designed to hybridize with cRNA of the human gene LIF 336cgtgacggac ttcccgccct tccacgccaa cggcacggag aaggccaagc 5033750DNAArtificial SequenceProbe SG337 Designed to hybridize with cRNA of the human gene LRP 337ctggaccagt cagaagccga gaaagctcgc aaggaacttt tggagctgga 5033850DNAArtificial SequenceProbe SG338 Designed to hybridize with cRNA of the human gene LSP1 338ggaccgagtc cctaaaccgc tccatagaga agagtaacag tgtgaagaaa 5033950DNAArtificial SequenceProbe SG339 Designed to hybridize with cRNA of the human gene LYL1 339agtgtctaca ttgggccagc aggacctttt agcatcttcc ctagcagccg 5034050DNAArtificial SequenceProbe SG340 Designed to hybridize with cRNA of the human gene NFKB1 340catccttccg caaactcagc tttaccgagt ctctgaccag tggtgcctca 5034150DNAArtificial SequenceProbe SG341 Designed to hybridize with cRNA of the human gene MAL 341caccttgatc atcctgtaca taattggagc ccacggtgga gagacttcct 5034250DNAArtificial SequenceProbe SG342 Designed to hybridize with cRNA of the human gene MAGEA1 342ctcctcccct cctctcctct cagctagtcc atgtttctcc aacacaagtt 5034350DNAArtificial SequenceProbe SG343 Designed to hybridize with cRNA of the human gene MAPK10 343agactaaaaa tggtgtagta aaaggacagc cttctccttc agcacaggtg 5034450DNAArtificial SequenceProbe SG344 Designed to hybridize with cRNA of the human gene MBP1 344ccatgcagag tctgtcctcc cagtcggtgc agcaaactca gggaagccat 5034550DNAArtificial SequenceProbe SG345 Designed to hybridize with cRNA of the human gene MCL1 345ggctcccagt gactactttt tgacttctgt ttgtcttacg cttctctcag 5034650DNAArtificial SequenceProbe SG346 Designed to hybridize with cRNA of the human gene MDM2 346tgaatctctc gactcagaag attatagcct tagtgaagaa ggacaagaac 5034750DNAArtificial SequenceProbe SG347 Designed to hybridize with cRNA of the human gene ABCB1 347tagctcgtgc ccttgttaga cagcctcata ttttgctttt ggatgaagcc 5034850DNAArtificial SequenceProbe SG348 Designed to hybridize with cRNA of the human gene ABCB4 348tagcgatttt tggaccaggc gatgatgcag tgaagcagca gaagtgcaac 5034950DNAArtificial SequenceProbe SG349 Designed to hybridize with cRNA of the human gene MEN1 349attgcctcag ccaagaccta ctatcgggat gaacacatct acccctacat 5035050DNAArtificial SequenceProbe SG350 Designed to hybridize with cRNA of the human gene CXCL9 350gaaggaactg attaaaaagt gggagaaaca ggtcagccaa aagaaaaagc 5035150DNAArtificial SequenceProbe SG351 Designed to hybridize with cRNA of the human gene MLF1 351ggggacaaac tccacatcaa aggctcatct gtgaaaagca acaaaaaata 5035250DNAArtificial SequenceProbe SG352 Designed to hybridize with cRNA of the human gene MLL 352gaaaacagga ccattgccca tagtccaaca tcttttacag aaagttcatc 5035350DNAArtificial SequenceProbe SG353 Designed to hybridize with cRNA of the human gene MMP9 353agtgagttga accaggtgga ccaagtgggc tacgtgacct atgacatcct 5035450DNAArtificial SequenceProbe SG354 Designed to hybridize with cRNA of the human gene NDUFB 354ccggaacaag agtatgttat ttaaaaggga attgcaaccc agtgaagaag 5035550DNAArtificial SequenceProbe SG355 Designed to hybridize with cRNA of the human gene MPO 355atcaccaccg tgtctaagaa caacatcttc atgtccaact catatccccg 5035650DNAArtificial SequenceProbe SG356 Designed to hybridize with cRNA of the human gene ABCC3 356ccaggtaaag caaatgaaat tgaaggactc gcgcatcaag ctgatgagtg 5035750DNAArtificial SequenceProbe SG357 Designed to hybridize with cRNA of the human gene ABCC5 357catcggtcct tctgtccaac gacagttccc gattctatgc catgtttgct 5035850DNAArtificial SequenceProbe SG358 Designed to hybridize with cRNA of the human gene MTCP1 358cagatacagc atcatttaat ggtcagggga gtacaggagc tgttgcttaa 5035950DNAArtificial SequenceProbe SG359 Designed to hybridize with cRNA of the human gene MTCP1 359gtgttgtgct cagtatccca agggaagatc tgtcgtctgt tcaggatttg 5036050DNAArtificial SequenceProbe SG360 Designed to hybridize with cRNA of the human gene MYOD1 360ttgccacaac ggacgacttc tatgacgacc cgtgtttcga ctccccggac 5036150DNAArtificial SequenceProbe SG361 Designed to hybridize with cRNA of the human gene MX1 361cgtcctgtcg gagccctgtc tctctctctg taataaactc atttctagca 5036250DNAArtificial SequenceProbe SG362 Designed to hybridize with cRNA of the human gene NINJ1 362agtacgacct taacaacccg gacaagcacg ccaagctgga cttcctcaac 5036350DNAArtificial SequenceProbe SG363 Designed to hybridize with cRNA of the human gene NPM1 363tagagtgatg gattgatacc tagcagcctg tgaaaaggaa tcagtgaatt 5036450DNAArtificial SequenceProbe SG364 Designed to hybridize with cRNA of the human gene IL32 364aggaggagct gacaccccag aagtgctctg aaccccaatc ctcaaaatga 5036550DNAArtificial SequenceProbe SG365 Designed to hybridize with cRNA of the human gene NUMA1 365ccccaacact cgcagtggaa cccgccgttc tccgcgcatt gccaccacca 5036650DNAArtificial SequenceProbe SG366 Designed to hybridize with cRNA of the human gene POU2F2 366ccaactggcc ccagtacaaa gatcaaggct gaagacccca gtggcgattc 5036750DNAArtificial SequenceProbe SG367 Designed to hybridize with cRNA of the human gene POU2F2 367tcccaagctt ccagcagtct gagcacaaca gttactacct tatcctcagc 5036850DNAArtificial SequenceProbe SG368 Designed to hybridize with cRNA of the human gene OGGI 368gaccccatcg aatgcctttt ctcttttatc tgttcctcca acaacaacat 5036950DNAArtificial SequenceProbe SG369 Designed to hybridize with cRNA of the human gene CDKN2B 369gcggatccca acggagtcaa ccgtttcggg aggcgcgcga tccaggtcat 5037050DNAArtificial SequenceProbe SG370 Designed to hybridize with cRNA of the human gene CDKN2A 370tgaggagcca gcgtctaggg cagcagccgc ttcctagaag accaggtcat 5037150DNAArtificial SequenceProbe SG371 Designed to hybridize with cRNA of the human gene CDKN2C 371ttagcctgat gcaggcaaac ggggctgggg gagccacaaa tcttcaataa 5037250DNAArtificial SequenceProbe SG372 Designed to hybridize with cRNA of the human gene CDKN1A 372gaggcccgtg agcgatggaa cttcgacttt gtcaccgaga caccactgga 5037350DNAArtificial SequenceProbe SG373 Designed to hybridize with cRNA of the human gene CDKN1B 373cctgcaaccg acgattcttc tactcaaaac aaaagagcca acagaacaga 5037450DNAArtificial SequenceProbe SG374 Designed to hybridize with cRNA of the human gene CDK5R1 374agaacctgaa gaagtcgctg tcgtgcgcca acctgtccac attcgcccag 5037550DNAArtificial SequenceProbe SG375 Designed to hybridize with cRNA of the human gene TOPORS 375aaccagccca gtaacattgt gtctcttcaa actgagccat caaggcaatt 5037650DNAArtificial SequenceProbe SG376 Designed to hybridize with cRNA of the human gene P55CDC 376ggatgcccat tcccaggtgt gctccatcct ctggtctccc cattacaagg 5037750DNAArtificial SequenceProbe SG377 Designed to hybridize with cRNA of the human gene CDKN1C 377cgcctgagaa gtcgtcgggc gatgtccccg cgccgtgtcc ctctccaagc 5037850DNAArtificial SequenceProbe SG378 Designed to hybridize with cRNA of the human gene TP73 378ctgcatcgag tatttcacct cccaagggtt acagagcatt taccacctgc 5037950DNAArtificial SequenceProbe SGD379 esigned to hybridize with cRNA of the human gene PAX5 379cccccccgct ggacagggca gctactcagc accgacgctg acagggatgg 5038050DNAArtificial SequenceProbe SG380 Designed to hybridize with cRNA of the human gene PBX1 380acagtccgca gggcatcagt gctaatggag gttggcagga tgctactacc 5038150DNAArtificial SequenceProbe SG381 Designed to hybridize with cRNA of the human gene PBX3 381ccaaattccg gttcttctgg ttcttttaac ctcccaaatt ctggggacat 5038250DNAArtificial SequenceProbe SG382 Designed to hybridize with cRNA of the human gene ENPP1 382aaacatctat gctgtcaaga ccgccgtgtc agtcacccag gggggccaca 5038350DNAArtificial SequenceProbe SG383 Designed to hybridize with cRNA of the human gene PCA1 383tcactggact cagcttctat caacaaagaa aagagccagt ttcagacatt 5038450DNAArtificial SequenceProbe SG384 Designed to hybridize with cRNA of the human gene PCNA 384gctcctgaag ccgaaaccag ctagactttc ctccttcccg cctgcctgta 5038550DNAArtificial SequenceProbe SG385 Designed to hybridize with cRNA of the human gene PDGFRB 385acgactatat catccccctg cctgacccca aacccgaggt tgctgacgag 5038650DNAArtificial SequenceProbe SG386 Designed to hybridize with cRNA of the human gene PRKCQ 386ggctgtcatt tgccgacaga gcactgatca acagcatgga ccagaatatg 5038750DNAArtificial SequenceProbe SG387 Designed to hybridize with cRNA of the human gene PLK1 387cctcagcaac ggcagcgtgc agatcaactt cttccaggat cacaccaagc 5038850DNAArtificial SequenceProbe SG388 Designed to hybridize with cRNA of the human gene PML 388actcaagaac ctggcccaga cctacctggc gagaaacatg agcgagcgca 5038950DNAArtificial SequenceProbe SG389 Designed to hybridize with cRNA of the human gene PRAME 389tttgatgagt gtgggatcac ggatgatcag ctccttgccc tcctgccttc 5039050DNAArtificial SequenceProbe SG390 Designed to hybridize with cRNA of the human gene PRKCI 390tctcagttta ctaatgaacc tgtccagctc actccagatg acgatgacat 5039150DNAArtificial SequenceProbe SG391 Designed to hybridize with cRNA of the human gene PTEN 391atattctgac accactgact ctgatccaga gaatgaacct tttgatgaag 5039250DNAArtificial SequenceProbe SG392 Designed to hybridize with cRNA of the human gene PTGS1 392gtacagctac gagcagttct tgttcaacac ctccatgttg gtggactatg 5039350DNAArtificial SequenceProbe SG393 Designed to hybridize with cRNA of the human gene PTHLH 393agtgactggg agtgggctag aaggggacca cctgtctgac acctccacaa 5039450DNAArtificial SequenceProbe SG394 Designed to hybridize with cRNA of the human gene SPI1 394gatctatacc aacgccaaac gcacgagtat tacccctatc tcagcagtga 5039550DNAArtificial SequenceProbe SG395 Designed to hybridize with cRNA of the human gene PTK2B 395ggagcgtgga tgatctcctg ccttccttgc cgtcatcttc acggacagag 5039650DNAArtificial SequenceProbe SG396 Designed to hybridize with cRNA of the human gene RAD51 396ggttccttga gcacccggaa acggtcacga gacccagagg aagaattata 5039750DNAArtificial SequenceProbe SG397 Designed to hybridize with cRNA of the human gene RAG1 397ggcaagctta ggggacccat taggcataga ggactctctg gaaagccaag 5039850DNAArtificial SequenceProbe SG398 Designed to hybridize with cRNA of the human gene RARA 398cagcttccag ttagtggata tagcacacca tccccagcca ccattgagac 5039950DNAArtificial SequenceProbe SG399 Designed to hybridize with cRNA of the human gene KRAS2 399gttgatgatg ccttctatac attagttcga gaaattcgaa aacataaaga 5040050DNAArtificial SequenceProbe SG400 Designed to hybridize with cRNA of the human gene RB1 400aactggcaga aatgacttct actcgaacac gaatgcaaaa gcagaaaatg 5040150DNAArtificial SequenceProbe SG401 Designed to hybridize with cRNA of the human gene VEGF 401aaatgttcct gcaaaaacac acactcgcgt tgcaaggcga ggcagcttga 5040250DNAArtificial SequenceProbe SG402 Designed to hybridize with cRNA of the human gene ZYX 402gaagaagttc ggccctgtgg tggccccaaa gcccaaagtg aatcccttcc 5040350DNAArtificial SequenceProbe SG403

Designed to hybridize with cRNA of the human gene CD28 403cccctatttc ccggaccttc taagcccttt tgggtgctgg tggtggttgg 5040450DNAArtificial SequenceProbe SG404 Designed to hybridize with cRNA of the human gene CD28 404caaaattgaa gttatgtatc ctcctcctta cctagacaat gagaagagca 5040550DNAArtificial SequenceProbe SG405 Designed to hybridize with cRNA of the human gene RBBP4 405ttctgtatca gaagacaata tcatgcaagt gtggcaaatg gcagagaaca 5040650DNAArtificial SequenceProbe SG406 Designed to hybridize with cRNA of the human gene DDX6 406tgtatgtggc agaataccac agcgagcctg tagaagatga gaaaccttaa 5040750DNAArtificial SequenceProbe SG407 Designed to hybridize with cRNA of the human gene APEX 407gcgccttgat tactttttgt tgtcccactc tctgttacct gcattgtgtg 5040850DNAArtificial SequenceProbe SG408 Designed to hybridize with cRNA of the human gene DPF2 408cagggcatcc atcttgcctc caatttaccc ccgtgatgat ggcggcagtg 5040950DNAArtificial SequenceProbe SG409 Designed to hybridize with cRNA of the human gene RGS1 409ctggcttgtg aagactataa gaaaacagag tctgatcttt tgccctgtaa 5041050DNAArtificial SequenceProbe SG410 Designed to hybridize with cRNA of the human gene HMMR 410tttgccctga agaccccatt aaaagaaggc aatacaaact gttaccgagc 5041150DNAArtificial SequenceProbe SG411 Designed to hybridize with cRNA of the human gene STAT5B 411tccttgacac cgatggggac ttcgatctgg aggacacaat ggacgtagcg 5041250DNAArtificial SequenceProbe SG412 Designed to hybridize with cRNA of the human gene BIRC5 412cgctttcctt tctgtcaaga agcagtttga agaattaacc cttggtgaat 5041350DNAArtificial SequenceProbe SG413 Designed to hybridize with cRNA of the human gene TAL1 413ttccccctat gagatggaga ttactgatgg tccccacacc aaagttgtgc 5041450DNAArtificial SequenceProbe SG414 Designed to hybridize with cRNA of the human gene NXF1 414tatggtgaag gaaaccgtag gtctggaaga ggcggttctg gtattcggtc 5041550DNAArtificial SequenceProbe SG415 Designed to hybridize with cRNA of the human gene TCL1A 415ttctggtgga gagaagtgag aataggcagc ccccaaataa aaaatattca 5041650DNAArtificial SequenceProbe SG416 Designed to hybridize with cRNA of the human gene TRA@ 416attattccag aagacacctt cttccccagc ccagaaagtt cctgtgatgt 5041750DNAArtificial SequenceProbe SG417 Designed to hybridize with cRNA of the human gene TCR beta 417cagccgtgta tctccgtgcc agcagcttca aaggtgccca ggccggttag 5041850DNAArtificial SequenceProbe SG418 Designed to hybridize with cRNA of the human gene DNTT 418ctgtatttgg agtggggctg aagacttctg agaagtggtt caggatgggt 5041950DNAArtificial SequenceProbe SG419 Designed to hybridize with cRNA of the human gene TERT 419attcctgctc aagctgactc gacaccgtgt cacctacgtg ccactcctgg 5042050DNAArtificial SequenceProbe SG420 Designed to hybridize with cRNA of the human gene ERBB4 420ttgacaaccc tgactactgg aaccacagcc tgccacctcg gagcaccctt 5042150DNAArtificial SequenceProbe SG421 Designed to hybridize with cRNA of the human gene ERBB2 421cacccagcac cttcaaaggg acacctacgg cagagaaccc agagtacctg 5042250DNAArtificial SequenceProbe SG422 Designed to hybridize with cRNA of the human gene EGFR 422cccagaaagg cagccaccaa attagcctgg acaaccctga ctaccagcag 5042350DNAArtificial SequenceProbe SG423 Designed to hybridize with cRNA of the human gene THPO 423cttctaaaca catcctacac ccactcccag aatctgtctc aggaagggta 5042450DNAArtificial SequenceProbe SG424 Designed to hybridize with cRNA of the human gene TIAM1 424aggaagtcat ttgggttagg cgtgaagact ttgccccctc caggaaactg 5042550DNAArtificial SequenceProbe SG425 Designed to hybridize with cRNA of the human gene TK1 425ggaagctctt tgccccacag cagattctgc aatgcagccc tgccaactga 5042650DNAArtificial SequenceProbe SG426 Designed to hybridize with cRNA of the human gene TNFRSF1A 426agaagtggga ggacagcgcc cacaagccac agagcctaga cactgatgac 5042750DNAArtificial SequenceProbe SG427 Designed to hybridize with cRNA of the human gene TOP2A 427gcctgatcct gccaaaacca agaatcgccg caaaaggaag ccatccactt 5042850DNAArtificial SequenceProbe SG428 Designed to hybridize with cRNA of the human gene FAIM3 428accagcctgc cgccatgatg gaggacagtg attcagatga ctacatcaat 5042950DNAArtificial SequenceProbe SG429 Designed to hybridize with cRNA of the human gene PLS3 429gtggcaatct aacagaagat gacaagcaca ataatgccaa gtatgcagtg 5043050DNAArtificial SequenceProbe SG430 Designed to hybridize with cRNA of the human gene TRADD 430cgccacctgc ccagactttt ctgttccagg gtcagcctgt agtgaatcgg 5043150DNAArtificial SequenceProbe SG431 Designed to hybridize with cRNA of the human gene TNFSF10 431gtaacaaatg agcacttgat agacatggac catgaagcca gttttttcgg 5043250DNAArtificial SequenceProbe SG432 Designed to hybridize with cRNA of the human gene TRAP 1 432aagtttgagg acaggtcccc agccgccgag tgcctatcag agaaggagac 5043350DNAArtificial SequenceProbe SG433 Designed to hybridize with cRNA of the human gene THBS1 433tagagtggtg atgtatgaag ggaagaaaat catggctgac tcaggaccca 5043450DNAArtificial SequenceProbe SG434 Designed to hybridize with cRNA of the human gene SUMO1 434atgtgattga agtttatcag gaacaaacgg ggggtcattc aacagtttag 5043550DNAArtificial SequenceProbe SG435 Designed to hybridize with cRNA of the human gene UVRAG 435gaagaaatca tcgggctgga agcacaggtt tcgcctcagg tgatcagcta 5043650DNAArtificial SequenceProbe SG436 Designed to hybridize with cRNA of the human gene VPREB1 436ctgtcctgct catgctgttt gtctactgca caggttgtgg tcctcagccg 5043750DNAArtificial SequenceProbe SG437 Designed to hybridize with cRNA of the human gene WNT16 437tggtgctgct atgtccgttg caggaggtgt gaaagcatga ctgatgtcca 5043850DNAArtificial SequenceProbe SG438 Designed to hybridize with cRNA of the human gene WT1 438accacagcac agggtacgag agcgataacc acacaacgcc catcctctgc 5043950DNAArtificial SequenceProbe SG439 Designed to hybridize with cRNA of the human gene XRCC3 439gacaccttgt tggagtgtgt gaataagaag gtccccgtac tgctgtctcg 5044050DNAArtificial SequenceProbe SG440 Designed to hybridize with cRNA of the human gene CCND3 440ttataccttt gccatgtacc cgccatccat gatcgccacg ggcagcattg 5044150DNAArtificial SequenceProbe SG441 Designed to hybridize with cRNA of the human gene CDK2 441accctttctt ccaggatgtg accaagccag taccccatct tcgactctga 5044250DNAArtificial SequenceProbe SG442 Designed to hybridize with cRNA of the human gene p14ARF 442aataaaataa ggggaatagg ggagcgggga cgcgagcagc accagaatcc 5044350DNAArtificial SequenceProbe SG443 Designed to hybridize with cRNA of the human gene HELLS 443gaccgagaaa gagctgttgt ggaagtgaat atccctgtag aatctgaagt 5044450DNAArtificial SequenceProbe SG444 Designed to hybridize with cRNA of the human gene GATA2 444tttcggcttc ccacccacgc cacccaaaga agtgtctcct gaccctagca 5044550DNAArtificial SequenceProbe SG445 Designed to hybridize with cRNA of the human gene GATA1 445atccggccca agaagcgcct gattgtcagt aaacgggcag gtactcagtg 5044650DNAArtificial SequenceProbe SG446 Designed to hybridize with cRNA of the human gene MLLT10 446ttaaattctc aacagctcac accagtacac aggcaccccc acttcacaca 5044750DNAArtificial SequenceProbe SG447 Designed to hybridize with cRNA of the human gene PICALM 447cggaaatgga accactaaga atgatgtaaa ttggagtcaa ccaggtgaaa 5044850DNAArtificial SequenceProbe SG448 Designed to hybridize with cRNA of the human gene KIT 448atgtatgaca taatgaagac ttgctgggat gcagatcccc taaaaagacc 5044950DNAArtificial SequenceProbe SG449 Designed to hybridize with cRNA of the human gene IL3RA 449gcctggagga gtgtctggtg actgaagtac aggtcgtgca gaaaacttga 5045050DNAArtificial SequenceProbe SG450 Designed to hybridize with cRNA of the human gene CEBPA 450aacgtggaga cgcagcagaa ggtgctggag ctgaccagtg acaatgaccg 5045150DNAArtificial SequenceProbe SG451 Designed to hybridize with cRNA of the human gene ITGA6 451agatccatgc tcagccatct gataaagaga ggcttacttc tgatgcatag 5045250DNAArtificial SequenceProbe SG452 Designed to hybridize with cRNA of the human gene CML66 452caggttgcta agcagcaagt agcaagccta gaaaccaatg atcctatttt 5045350DNAArtificial SequenceProbe SG453 Designed to hybridize with cRNA of the human gene TRAF3 453actggagaga tgaatatcgc ctctggctgc ccagtctttg tggcccaaac 5045450DNAArtificial SequenceProbe SG454 Designed to hybridize with cRNA of the human gene DAPK1 454ccttttgctg aaggcatcct ctgtgttcaa aatcaacctg gatggcaatg 5045550DNAArtificial SequenceProbe SG455 Designed to hybridize with cRNA of the human gene MAP3K12 455cttcccggcc tgcaaccccc aaaatggatt ctgcgaggat gacaatgttt 5045650DNAArtificial SequenceProbe SG456 Designed to hybridize with cRNA of the human gene PRKDC 456ttaggattaa ttgagtggct tgaaaatact gttaccttga aggaccttct 5045750DNAArtificial SequenceProbe SG457 Designed to hybridize with cRNA of the human gene DNMT3B 457ggcggaagcc catgcaacga tctctcaaat gtgaatccag ccaggaaagg 5045850DNAArtificial SequenceProbe SG458 Designed to hybridize with cRNA of the human gene GSTP1 458cctcccctga gtacgtgaac ctccccatca atggcaacgg gaaacagtga 5045950DNAArtificial SequenceProbe SG459 Designed to hybridize with cRNA of the human gene HLA-DRA 459agccctgtgg aactgagaga gcccaacgtc ctcatctgtt tcatcgacaa 5046050DNAArtificial SequenceProbe SG460 Designed to hybridize with cRNA of the human gene HOXA10 460tcccttcgcc aaattatccc acaacaatgt catcgtcgga gagccccgcc 5046150DNAArtificial SequenceProbe SG461 Designed to hybridize with cRNA of the human gene IRF8 461ggatatggcc cccttgcgct ccaaactcat tctcgtgcag attgagcagc 5046250DNAArtificial SequenceProbe SG462 Designed to hybridize with cRNA of the human gene ID2 462aattcccttc tgagttaatg tcaaatgaca gcaaagcact gtgtggctga 5046350DNAArtificial SequenceProbe SG463 Designed to hybridize with cRNA of the human gene ACTB 463tgatgatatc gccgcgctcg tcgtcgacaa cggctccggc atgtgcaagg 5046450DNAArtificial SequenceProbe SG464 Designed to hybridize with cRNA of the human gene ACTB 464acgttgctat ccaggctgtg ctatccctgt acgcctctgg ccgtaccact 5046550DNAArtificial SequenceProbe SG465 Designed to hybridize with cRNA of the human gene GRK4 465atggtgaaac cccgtctcta ctaaaaatac aaaaattagc cgggcgtggt 5046650DNAArtificial SequenceProbe SG466 Designed to hybridize with cRNA of the human gene GAPD 466tgcttttaac tctggtaaag tggatattgt tgccatcaat gaccccttca 5046750DNAArtificial SequenceProbe SG467 Designed to hybridize with cRNA of the human gene GAPD 467gtctcctctg acttcaacag cgacacccac tcctccacct ttgacgctgg 5046850DNAArtificial SequenceProbe SG468 Designed to hybridize with cRNA of the human gene STAT1 468atccaaatat tgacaaagac catgcctttg gaaagtatta ctccaggcca 5046950DNAArtificial SequenceProbe SG469 Designed to hybridize with cRNA of the human gene 18S rRNA 469ttgactatct agaggaagta aaagtcgtaa caaggtttcc gtaggtgaac 5047050DNAArtificial SequenceProbe SG470 Designed to hybridize with cRNA of the human gene TFRC 470ccagctttac tggagaactt gaaactgcgt aaacaaaata acggtgcttt 5047150DNAArtificial SequenceProbe SG471 Designed to hybridize with cRNA of the human gene 28S rRNA 471tctccccttc cttggtgcct tctcggctct tgacacttag ccgctgtctc 5047250DNAArtificial SequenceProbe SG472 Designed to hybridize with cRNA of the human gene RPL37A 472tcacggtaaa gtccgccatc agaagactga aggagttgaa agaccagtag 5047350DNAArtificial SequenceProbe SG473 Designed to hybridize with cRNA of the human gene RPL41 473tggaggaaga agcgaatgcg caggctgaag cgcaaaagaa gaaagatgag 5047450DNAArtificial SequenceProbe SG474 Designed to hybridize with cRNA of the human gene HNRPL 474acccttacac tctgaagttg tgtttctcca ctgctcagca cgcctcctaa 5047550DNAArtificial SequenceProbe SG475 Designed to hybridize with cRNA of the human gene ILF2 475ctatcttgct tctgaaatat ctacctggga tggagtgata gtaacacctt 5047650DNAArtificial SequenceProbe SG476 Designed to hybridize with cRNA of the human gene TAGLN2 476gttccctaag aaatccaagg agaatcctcg gaacttctca gataaccagc 5047750DNAArtificial SequenceProbe SG477 Designed to hybridize with cRNA of the human gene CANP2 477aaggcattag aagaagcagg tttcaagatg ccctgtcaac tccaccaagt 5047850DNAArtificial SequenceProbe SG478 Designed to hybridize with cRNA of the human gene PSMA5 478accacaagtc tatgactttg aaagaagcca tcaagtcttc actcatcatc 5047950DNAArtificial SequenceProbe SG479 Designed to hybridize with cRNA of the human gene PMM1 479atccacttct ttgggaacga gactagccct ggtgggaacg actttgagat 5048050DNAArtificial SequenceProbe SG480 Designed to hybridize with cRNA of the human gene MLF2 480aatacgggtg atggtgcccc caaggtctac caagagacat cagagatgcg 5048150DNAArtificial SequenceProbe SG481 Designed to hybridize with cRNA of the human gene PPP1CC 481gagacctgta acgcctccaa ggggtatgat cacaaagcaa gcaaagaaat 5048250DNAArtificial SequenceProbe SG482 Designed to hybridize with cRNA of the human gene CASC3 482atcacaggta tatggaggag tgacctacta taaccccgcc cagcagcagg 5048350DNAArtificial SequenceProbe SG483 Designed to hybridize with cRNA of the human gene KIAA0864 483tgccttacca tctctgccac ctgtggaatc gctgagagat tgccagaagc 5048450DNAArtificial SequenceProbe SG484 Designed to hybridize with cRNA of the human gene TXNRD1 484gccattggaa tggacgattc cgtcaagaga taacaacaaa tgttatgcaa 5048550DNAArtificial SequenceProbe SG485 Designed to hybridize with cRNA of the human gene PSMD7 485tgcacaacct catcaacaac aagattgcca accgggatgc agagaagaaa 5048650DNAArtificial SequenceProbe SG486 Designed to hybridize with cRNA of the human gene EIF2B2 486caccttccta catctaccgc ctgatgagtg aactctacca tcctgatgat 5048750DNAArtificial SequenceProbe SG487 Designed to hybridize with cRNA of the human gene HLA-A 487tagaaaagga gggagctact ctcaggctgc aagcagtgac agtgcccagg 5048850DNAArtificial SequenceProbe SG488 Designed to hybridize with cRNA of the human gene MCM7 488ggcagcttca atcgccccag aaatatacgg gcatgaagat gtgaagaagg 5048950DNAArtificial SequenceDProbe SG489 esigned to hybridize with cRNA of the human gene TNFRSF25 489ctgacctaca cataccgcca ctgctggcct cacaagcccc tggttactgc 5049050DNAArtificial SequenceProbe SG490 Designed to hybridize with cRNA of the human gene LGALS3 490agtacaatca tcgggttaaa aaactcaatg aaatcagcaa actgggaatt 5049150DNAArtificial SequenceProbe SG491 Designed to hybridize with cRNA of the human gene HLA-DPA1 491gaacagatta cagcttccac aagttccatt acctgacctt tgtgccctca 5049250DNAArtificial SequenceProbe SG492 Designed to hybridize with cRNA of the human gene PLAU 492ctcgtctgtt ccctccaagg ccgcatgact ttgactggaa ttgtgagctg 5049350DNAArtificial SequenceProbe SG493 Designed to hybridize with cRNA of the human gene COL3A1 493tcgaggattc cctggtaatc caggtgcccc aggttctcca ggccctgctg 5049450DNAArtificial SequenceProbe SG494 Designed to hybridize with cRNA of the human gene ANK2 494ctcagttcct gaggacatct ttgacacaag gcccatttgg gatgagtcta 5049550DNAArtificial SequenceProbe SG495 Designed to hybridize with cRNA of the human gene SERPINA9 495gcacctctat tgcagaatta caataacaca ttcaataaaa ctaaaatatg 5049650DNAArtificial SequenceProbe SG496 Designed to hybridize with cRNA of the human gene NPM3 496ggcaccagat tgttacgatg agcaatgatg tttctgagga ggagagcgag 5049750DNAArtificial SequenceProbe SG497 Designed to hybridize with cRNA of the human gene CCR6 497gcagaccagt gagaccgcag ataacgacaa tgcgtcgtcc ttcactatgt 5049850DNAArtificial SequenceProbe SG498 Designed to hybridize with cRNA of the human gene HCK 498ccgagctgcc aacatcttgg tctctgcatc cctggtgtgt aagattgctg 5049950DNAArtificial SequenceProbe SG499 Designed to hybridize with cRNA of the human gene GNL3 499aggacataca tgaagaattg ccaaaacgga aagaaaggaa gcaggaggag 5050050DNAArtificial SequenceProbe SG500 Designed to hybridize with cRNA of the human gene GRB2 500ccggcatgtt tccccgcaat tatgtcaccc ccgtgaaccg gaacgtctaa 5050150DNAArtificial SequenceProbe SG501 Designed to hybridize with cRNA of the human gene BCL2A1 501ggagttcata atgaataaca caggagaatg gataaggcaa aacggaggct 5050250DNAArtificial SequenceProbe SG502 Designed to hybridize with cRNA of the human gene ELF1 502gtttagaggt ctaatgctat gttttcatat tacagagtga atttgtattt 5050350DNAArtificial SequenceProbe SG503 Designed to hybridize with cRNA of the human gene CTSB

503tgctctacaa gtcaggagtg taccaacacg tcaccggaga gatgatgggt 5050450DNAArtificial SequenceProbe SG504 Designed to hybridize with cRNA of the human gene GCET2 504atcctggttc tctctcttcc tccatctgtg actttgaaca tgctacttgg 5050550DNAArtificial SequenceProbe SG505 Designed to hybridize with cRNA of the human gene FN1 505tcgtgctttg acccctacac agtttcccat tatgccgttg gagatgagtg 5050650DNAArtificial SequenceProbe SG506 Designed to hybridize with cRNA of the human gene PDCD1 506ttcctagcgg aatgggcacc tcatcccccg cccgcagggg ctcagccgac 5050750DNAArtificial SequenceProbe SG507 Designed to hybridize with cRNA of the human gene HLA-DRB3 507gttcatctac ttcaggaatc agaaaggaca ctctggactt cagccaacag 5050850DNAArtificial SequenceProbe SG508 Designed to hybridize with cRNA of the human gene HLA-DQA1 508gcagtcagtc acagaagatg tttctgagac cagcttcctc tccaagagtg 5050950DNAArtificial SequenceProbe SG509 Designed to hybridize with cRNA of the human gene GCET2 509ggtgaaggct ccacaaacct gtgacacatg caagctcaag ccattgcatt 5051050DNAArtificial SequenceProbe SG510 Designed to hybridize with cRNA of the human gene SERPNINA9 510ggagccccaa ggaatgaaat atggtaaccc agcaacatcc catgaagcta 5051150DNAArtificial SequenceProbe SG511 Designed to hybridize with cRNA of the human gene CDKN3 511ctgcacatct atcatcaaga gattcacaat caagatctgt atcaagataa 5051250DNAArtificial SequenceProbe SG512 Designed to hybridize with cRNA of the human gene ELF1 512cttctctcaa gcttcttggc cttcaagtat tctttctcta tcgtcttttg 5051350DNAArtificial SequenceProbe SG513 Designed to hybridize with cRNA of the human gene CATSD 513gtgccgctga ttcagggcga gtacatgatc ccctgtgaga aggtgtccac 5051450DNAArtificial SequenceProbe SG514 Designed to hybridize with cRNA of the human gene HSPB1 514atggctacat ctcccggtgc ttcacgcgga aatacacgct gccccccggt 5051550DNAArtificial SequenceProbe SG515 Designed to hybridize with cRNA of the human gene ACTN1 515cccctacaca accatcacgc ctcaggagat caatggcaaa tgggaccacg 5051650DNAArtificial SequenceProbe SG516 Designed to hybridize with cRNA of the human gene BMP6 516gaaccccgag tatgtcccca aaccgtgctg tgcgccaact aagctaaatg 5051750DNAArtificial SequenceProbe SG517 Designed to hybridize with cRNA of the human gene FAM38A 517gtctgtggtc atccccaatc tcttccccaa gtacatccgt gcccccaacg 5051850DNAArtificial SequenceProbe SG518 Designed to hybridize with cRNA of the human gene CD48 518ttatacttgc caagtcagca attctgtgag cagcaagaat ggcaccgtct 5051950DNAArtificial SequenceProbe SG519 Designed to hybridize with cRNA of the human gene IL4R 519tcacagtggg agaagcggtc ccgaggccag gaaccagcca agtgcccaca 5052050DNAArtificial SequenceProbe SG520 Designed to hybridize with cRNA of the human gene DRP2 520ccagtgtgcg aagttctgat gtgactgcca acaccctgct ggcctcttga 5052150DNAArtificial SequenceProbe SG521 Designed to hybridize with cRNA of the human gene JUNB 521ggaggacaag gtgaagacgc tcaaggccga gaacgcgggg ctgtcgagta 5052250DNAArtificial SequenceProbe SG522 Designed to hybridize with cRNA of the human gene S100A8 522aattgctaga gaccgagtgt cctcagtata tcaggaaaaa gggtgcagac 5052350DNAArtificial SequenceProbe SG523 Designed to hybridize with cRNA of the human gene ZNFN1A1 523agttggaggc attcgacttc ctaacggaaa actaaagtgt gatatctgtg 5052450DNAArtificial SequenceProbe SG524 Designed to hybridize with cRNA of the human gene MERTK 524tcattgcccg atgaactttt gtttgctgac gactcctcag aaggctcaga 5052550DNAArtificial SequenceProbe SG525 Designed to hybridize with cRNA of the human gene KLF13 525tgcctagtgc tgaggcctct ggggctggaa agcctcagca gaaaggaggc 5052650DNAArtificial SequenceProbe SG526 Designed to hybridize with cRNA of the human gene CBFB 526aatttcccct gagggaatcg ctttttaagt gatccttaca gtggtgtttt 5052750DNAArtificial SequenceProbe SG527 Designed to hybridize with cRNA of the human gene CEBPB 527tcctctccga cctcttctcc gacgactacg ggggcaagaa ctgcaagaag 5052850DNAArtificial SequenceProbe SG528 Designed to hybridize with cRNA of the human gene CEBPD 528cggggcggga gagactcagc aacgacccat acctcagacc cgacggcccg 5052950DNAArtificial SequenceProbe SG529 Designed to hybridize with cRNA of the human gene TFCP2 529ctgcagttga gggagcagca acaacagcag cagcaacagc agcagaagca 5053050DNAArtificial SequenceProbe SG530 Designed to hybridize with cRNA of the human gene CREB1 530cgcctgtaat cccagcactt tgggaggcca aggtgggtgg atcacctgtg 5053150DNAArtificial SequenceProbe SG531 Designed to hybridize with cRNA of the human gene NFIC 531gcggcgatta ctacacttcg cccagctcgc ccacgagtag cagccgcaac 5053250DNAArtificial SequenceProbe SG532 Designed to hybridize with cRNA of the human gene GABPB2 532tgctccattg tccaattctt cagaaactcc agtagtggcc acagaagaag 5053350DNAArtificial SequenceProbe SG533 Designed to hybridize with cRNA of the human gene EGR1 533gatggcttga catgtgcaat tgtgagggac atgctcacct ctagccttaa 5053450DNAArtificial SequenceProbe SG534 Designed to hybridize with cRNA of the human gene KLF1 534gccactaccg gaaacacacg gggcagcgcc ccttccgctg ccagctctgc 5053550DNAArtificial SequenceProbe SG535 Designed to hybridize with cRNA of the human gene ELF1 535tatggctgac cctgtttcag aagcaggata gtataaaagc atcagcctaa 5053650DNAArtificial SequenceProbe SG536 Designed to hybridize with cRNA of the human gene ETS1 536ctcgagctgg ccccagactt tgttggggac atcttatggg aacatctaga 5053750DNAArtificial SequenceProbe SG537 Designed to hybridize with cRNA of the human gene ETS2 537tatttgaaat aagaattcag acatctgagg ttttatttca tttttcaata 5053850DNAArtificial SequenceProbe SG538 Designed to hybridize with cRNA of the human gene FLI1 538attcgcaagt gctgtgcgct tgtcagacca tcagaccagg gccaaccaat 5053950DNAArtificial SequenceProbe SG539 Designed to hybridize with cRNA of the human gene GATA3 539gagccctgct cgatgctcac agggccccca gcgagagtcc ctgcagtccc 5054050DNAArtificial SequenceProbe SG540 Designed to hybridize with cRNA of the human gene CBFA2T1 540tgttggacaa atgtgaagat gcattgtagt ttaaccatat gcccacattt 5054150DNAArtificial SequenceProbe SG541 Designed to hybridize with cRNA of the human gene HIF1A 541atgcattctt agcaaaattg cctagtatgt taatttgctc aaaatacaat 5054250DNAArtificial SequenceProbe SG542 Designed to hybridize with cRNA of the human gene TCF1 542cccgagcagc tgagcagggc cggggaactg gccaagctga ggtgcccagg 5054350DNAArtificial SequenceProbe SG543 Designed to hybridize with cRNA of the human gene HOXD8 543caaatttccc gtttcccggc aggaggtgaa ggacggggaa acgaaaaagg 5054450DNAArtificial SequenceProbe SG544 Designed to hybridize with cRNA of the human gene HOXD9 544cctcagcttg cagcgaccac ccgatcccag gctgttcgct gaaggaggag 5054550DNAArtificial SequenceProbe SG545 Designed to hybridize with cRNA of the human gene MAFB 545agcgctccta gggtgagagg cttagccatc cctgaccctg gcagtgcact 5054650DNAArtificial SequenceProbe SG546 Designed to hybridize with cRNA of the human gene MAFK 546gcggcgggca ggcgggtggg ggcacacccc tcgtacctgt cactgggatg 5054750DNAArtificial SequenceProbe SG547 Designed to hybridize with cRNA of the human gene EDF1 547ttggccgcca gttccgttct cctcacgggc cgaacggaac aaggggtcca 5054850DNAArtificial SequenceProbe SG548 Designed to hybridize with cRNA of the human gene ELF4 548ctagatgggg tccaccccca ttcctgctca agcatgggca cctaccacat 5054950DNAArtificial SequenceProbe SG549 Designed to hybridize with cRNA of the human gene ZNF42 549tccgcgtaca cacgggcgag aaaccctttg cctgccccga gtgtggccag 5055050DNAArtificial SequenceProbe SG550 Designed to hybridize with cRNA of the human gene NF1 550ggaattgatg aagaaaccag tgaagaatcc ctcctgactc ccacatctcc 5055150DNAArtificial SequenceProbe SG551 Designed to hybridize with cRNA of the human gene NFATC1 551ttctcgtctc acgcagttcg aggaggaccc tagaaagcca ggagctgtga 5055250DNAArtificial SequenceProbe SG552 Designed to hybridize with cRNA of the human gene PAX6 552ggtgtgtcag ttccagttca agttcccgga agtgaacctg atatgtctca 5055350DNAArtificial SequenceProbe SG553 Designed to hybridize with cRNA of the human gene PAX8 553gcaccacccc aggtcctcct gcagtgcggc atccccttgg cagctgccgt 5055450DNAArtificial SequenceProbe SG554 Designed to hybridize with cRNA of the human gene PLP 554gccagtgatg gtgggtgggg gctgggcctt ccccgccacc tccacccctg 5055550DNAArtificial SequenceProbe SG555 Designed to hybridize with cRNA of the human gene PLZF 555gtgctccctc tcactggtgg ggcgtggctt cctcacagag agggacgaca 5055650DNAArtificial SequenceProbe SG556 Designed to hybridize with cRNA of the human gene RBP4 556gtacaggctg atcgtccaca acggttactg cgatggcaga tcagaaagaa 5055750DNAArtificial SequenceProbe SG557 Designed to hybridize with cRNA of the human gene RORA 557cagacctgga gcgccacaca ctgcacatct tttggtgatc ggggtcaggc 5055850DNAArtificial SequenceProbe SG558 Designed to hybridize with cRNA of the human gene SP1 558cctgcttccc cttcctaagt ctgtcatcct ctggaaggga tgggtggtgc 5055950DNAArtificial SequenceProbe SG559 Designed to hybridize with cRNA of the human gene STAT1 559atatcaatag aaggatgtac atttccaaat tcacaagttg tgtttgatat 5056050DNAArtificial SequenceProbe SG560 Designed to hybridize with cRNA of the human gene TBP 560tgcagggtgt ggcaccaggt gatgcccttc tgtaagtgcc caccgcggga 5056150DNAArtificial SequenceProbe SG561 Designed to hybridize with cRNA of the human gene TCF7 561aagggctgcc gggccaggcg cggtggctca cgcctgtaat cccagcactt 5056250DNAArtificial SequenceProbe SG562 Designed to hybridize with cRNA of the human gene ETV7 562cagccattgc ttgggaaggc tgggaggcct cccatccagg acactggggg 5056350DNAArtificial SequenceProbe SG563 Designed to hybridize with cRNA of the human gene ZAP70 563cgcggaagga gcagggcaca tacgccctgt ccctcatcta tgggaagacg 5056455DNAArtificial SequenceNegative control 564ggggaaagaa agatcgatga gaaagaggaa cggggattga caggaatgaa gaagg 5556550DNAArtificial SequenceNegative control 565cgtctcggtg aactcaagtg aatcaaggga agagaattcc taactgcacg 5056655DNAArtificial SequenceNegative control 566tcagcttcct ttctcccttt cctccttcct tccttctcac catcctgtcc ttttt 5556755DNAArtificial SequenceNegative control 567gaggaaacag gaaagaagag gaaggaagga agacagggaa gaaaagaggg aggga 5556854DNAArtificial SequenceNegative control 568tctgtgggga ggggttgttt tggggttgtt tttgtttttt cttgccaggt agat 5456955DNAArtificial SequenceNegative control 569ctctctctct ctctctctct ctctctgtct ctccccacct ctctcacatc ccttg 5557050DNAArtificial SequenceNegative control 570tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tggtgttgtg tgtgtttgtg 5057125DNAArtificial SequenceNegative control 571gtcgtcaaga tgctaccgtt cagga 2557250DNAArtificial SequencePositive hybridization control 572aggccgtgaa gatatattca tcagctacca tgcgaaagac gatgtccaaa 5057350DNAArtificial SequencePositive hybridization control 573cgagccaggc aaagcggagt aactcagttc gaagtaaggg gaaaatgtcg 5057450DNAArtificial SequenceGives rise to non-specific hybridization 574gcttttcttc gtttatcatc accatcacca tcatcatcat catcatcatc 5057550DNAArtificial SequenceNegative control 575gccaggatct caaacccacc aaaccgttcc agaatcatgg accgctttcg 5057650DNAArtificial SequencePositive hybridization control 576gtccaagcga gaagatactt aacaatatca acattaccat taccagcaga 5057750DNAArtificial SequenceNegative control 577atcccgatgc aaaaggcgga cgacaaggac tacggtctag aagctctgga 5057850DNAArtificial SequencePositive hybridization control 578ccacatcacc ttcaccattt ttcttcttcg ttgattctct gtttgtgttt 5057950DNAArtificial SequenceGives rise to non-specific hybridization 579tcctctgttt tgctcttgcc ttatccgctg cttctctctc cctctctttc 5058050DNAArtificial SequenceNegative control 580tgtgacacga cctacaacaa tggctgcaac ggtggtctca tggactatgc 5058150DNAArtificial SequencePositive hybridization control 581agaataataa atgaagtgat gatgattgat gattgatgat tgatgattat 5058250DNAArtificial SequencePositive hybridization control 582agtgacaagt ttcgctgatt atagtggtta atgctggtct tatcttcgtc 5058350DNAArtificial SequencePositive hybridization control 583atgggcggtg cggggttgat gttgacgacg gtgtggctgc ggttgggtat 5058450DNAArtificial SequenceActs as positive internal process control spiked control 584cctcaacgcc tacaaaagcc agtttatccc gtcaaaggat tccgtttcta 5058550DNAArtificial SequenceActs as positive internal process control spiked control 585cgttatacgg aagatgatga accgcttcat gccactgaat acgttgaaaa 5058650DNAArtificial SequenceActs as positive internal process control spiked control 586ctaccaagtg gctaaacgga ccgcagattt gtacggaaaa gaaatgcctc 5058750DNAArtificial SequenceActs as positive internal process control spiked control 587aacacaagcg gtttccacca tgtccacaag aaaggggagg taacaccagg 5058850DNAArtificial SequenceActs as positive internal process control spiked control 588gccagcaaca actcaaccag caacaaaacc agtttcacag gtgtcaggac 5058950DNAArtificial SequenceActs as positive internal process control spiked control 589aagcagattc agtagcagat gccgttcaaa aggtcgattt aagtagaagt 5059050DNAArtificial SequenceActs as positive internal process control spiked control 590gacttcctga tattgttgat acatgcggaa cagggggaga cggtatttcc 5059170DNAArtificial SequenceAntisense oligonucleotide C2 complementary to SCN2. Biotin residue at 5' 591acgctataaa catccactac cgacattttc cccttacttt gaactgagtt actccgcttt 60gcctggctcg 7059270DNAArtificial SequenceAntisense oligonucleotide C3 complementary to SCN3.Biotin residue at 5' 592gagcgaaccg gcgtaagttg tttggacatc gtctttcgca tggtagctga tgaatatatc 60ttcacggcct 7059370DNAArtificial SequenceAntisense oligonucleotide C6 complementary to SCN6. Biotin residue at n 5' 593atcatacgcc acttcatgtt tctgctggta atggtaatgt tgatattgtt aagtatcttc 60tcgcttggac 7059470DNAArtificial SequenceAntisense oligonucleotide C8 complementary to SCN8. Residue of biotin at 5' 594actgaaaaca gaacaaacac aaacacaaac agagaatcaa cgaagaagaa aaatggtgaa 60ggtgatgtgg 7059570DNAArtificial SequenceAntisense oligonucleotide C11 complementary to SCN11. Residue of biotin at 5' 595aacattcaag catgatgatg ataatcatca atcatcaatc atcaatcatc atcacttcat 60ttattattct 7059670DNAArtificial SequenceAntisense oligonucleotide C12 complementary to SCN12. Residue of biotin at 5' 596ttaggattct aaatagtagc gacgaagata agaccagcat taaccactat aatcagcgaa 60acttgtcact 7059770DNAArtificial SequenceAntisense oligonucleotide C13 complementary to SCN13. Residue of biotin at 5' 597tctgaaggct tgcttgatcc atacccaacc gcagccacac cgtcgtcaac atcaaccccg 60caccgcccat 7059824DNAArtificial SequencePrimer PSMB4_Forward of Gene PSMB4 598ttctgggaga tggacacagc tata 2459921DNAArtificial SequencePrimer PSMB4_Reverse of Gene PSMB4 599ccacaaaggg ttcatcttcg a 2160021DNAArtificial SequencePrimer CD23A_Forward of Gene CD23A 600tgccctgaaa agtggatcaa t 2160121DNAArtificial SequencePrimer CD23A_Reverse of Gene CD23A 601ccatgtcgtc acaggcatac c 2160221DNAArtificial SequencePrimer LCP1_Forward of Gene LCP1 602ccaggtaccc ttctcgcttt t 2160320DNAArtificial SequencePrimer LCP1_Reverse of Gene LCP1 603ctcctggccc tcatcttgaa 2060424DNAArtificial SequencePrimer ABCC5_Forward of Gene ABCC5 604ccctcaaagt ctgcaacttt aagc 2460521DNAArtificial SequencePrimer ABCC5_Reverse of Gene ABCC5 605acacaccaaa ccacacagca a 2160621DNAArtificial SequencePrimer POU2F2_Forward of Gene POU2F2 606gaggaccagc atcgagacaa a 2160720DNAArtificial SequencePrimer POU2F2_Reverse of Gene POU2F2 607aaccagacgc ggatcacttc 20

Claims

1. A composition which comprises at least one oligonucleotide from the group composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, or combinations thereof, to be used as probe in the determination of the expression level of a gene which possesses a sequence complementary to said oligonucleotide by the evaluation of the mRNA level corresponding to that gene, of application in the in vitro diagnosis of neoplasias originating from hematopoietic cells and/or in the in vitro prognosis of the evolution of said disease.

2. A composition according to claim 1, which comprises at least the oligonucleotides SG117, SG428, SG459, SG507, SG508.

3. A composition according to claim 2, which additionally comprises at least oligonucleotides SG461 and SG493.

4. A composition according to claim 2, which additionally comprises at least the oligonucleotide SG237.

5. A composition according to claim 4, which additionally comprises at least one oligonucleotide selected from the group of SG2, SG4, SG8, SG10, SG13, SG15, SG16, SG19, SG20, SG23, SG26, SG28, SG31, SG34, SG36, SG39, SG48, SG58, SG60, SG65, SG76, SG77, SG84, SG89, SG94, SG9, SG97, SG99, SG102, SG106, SG107, SG463, SG115, SG116, SG120, SG129, SG134, SG135, SG138, SG139, SG141, SG145, SG158, SG161, SG163, SG176, SG178, SG185, SG207, SG208, SG210, SG217, SG227, SG231, SG237, SG264, SG272, SG277, SG281, SG283, SG286, SG294, SG298, SG299, SG307, SG308, SG319, SG328, SG330, SG333, SG336, SG342, SG344, SG345, SG347, SG361, SG384, SG389, SG395, SG404, SG407, SG416, SG423, SG430, SG432, SG434, SG444, SG446, SG453, SG458, SG464, SG465, SG466, SG467, SG471, SG473, SG474, SG475, SG481, SG485, SG487, SG491, SG498, SG511, SG517, SG518, SG522, SG526, SG530, SG533, SG538, SG541, SG554, SG558, SG561 or combinations thereof.

6. A composition according to claim 2, to be used in the in vitro diagnosis of chronic lymphatic leukemia.

7. A composition according to claim 1, which comprises at least oligonucleotides SG26, SG216, SG366.

8. A composition according to claim 7, which additionally comprises at least one oligonucleotide selected from the group of SG31, SG177, SG194, SG195, SG197, SG213, SG293, SG301, SG309, SG333, SG343, SG357, SG439, SG452, SG555, SG556.

9. A composition according to claim 7, to be used in the in vitro prognosis of the future evolution of the disease in a patient suffering from chronic lymphatic leukemia.

10. A composition according to claim 1, which comprises the totality of the nucleotides of the group composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438; SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563.

11. A composition according to claim 1, characterized in that it additionally comprises at least one oligonucleotide selected from the group composed of SG463, SG464, SG466, SG467, SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6, SSPC7, SCN1, SCN2, SCN3, SCN5, SCN6, SCN7, SCN8, SCN10, SCN11, SCN12, SCN13, SC1, SC2, SC3, SC4, SC5, SC6 and SC7.

12. A composition according to claim 11, which comprises all the oligonucleotides from the group composed of SG463, SG464, SG466, SG467, SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6, SSPC7, SCN1, SCN2, SCN3, SCN5, SCN6, SCN7, SCN8, SCN10, SCN11, SCN12, SCN13, SC1, SC2, SC3, SC4, SC5, SC6 and SC7.

13. A composition according to claim 1, wherein the oligonucleotides are disposed on a solid support.

14. A composition according to claim 13, wherein the oligonucleotides are disposed in an ordered fashion on a solid support which is glass similar to a slide whereto the oligonucleotides are bound by covalent bonds, forming a microarray.

15. A composition in the form of microarray according to claim 14, which comprises the totality of the oligonucleotides from the group composed of SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563.

16. A composition in the form of microarray according to claim 15, which additionally comprises at least one pair of oligonucleotides selected from that composed of the oligonucleotides SG463 and SG464 and that composed of the oligonucleotides SG466 and SG467, at least one oligonucleotide from the group composed of SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6 and SSPC7, at least one oligonucleotide from the group composed of SCN2, SCN3, SCN6, SCN8, SCN11, SCN12 and SCN13 and at least one oligonucleotide from the group composed of SC1, SC2, SC3, SC4, SC5, SC6, SC7, SCN1, SCN5, SCN7 and SCN10.

17. A composition in the form of microarray according to claim 16, which comprises the totality of the oligonucleotides from the group composed of SG463, SG464, SG466, SG467, SSPC1, SSPC2, SSPC3, SSPC4, SSPC5, SSPC6, SSPC7, SCN2, SCN3, SCN6, SCN8, SCN11, SCN12, SCN13, SC1, SC2, SC3, SC4, SC5, SC6, SC7, SCN1, SCN5, SCN7 and SCN10.

18. A composition in the form of microarray according to claim 17, which additionally comprises points lacking oligonucleotides wherein the solvent wherein the oligonucleotides are found on being deposited on said glass is bound to the glass.

19. A composition in the form of microarray according to claim 18, which comprises at least twelve copies of each one of the different oligonucleotides present therein, as well as at least twelve points lacking oligonucleotides wherein the solvent wherein the oligonucleotides are found on being deposited on said glass is bound to the glass.

20. A composition in the form of microarray according to claim 18, wherein in the points lacking oligonucleotides the DMSO solvent is bound to the glass.

21. A composition in the form of microarray according to claim 15 to be used in the in vitro diagnosis of chronic lymphatic leukemia and/or for the in vitro prognosis of the evolution of said disease.

22. A device for the in vitro diagnosis of a neoplasia originating from hematopoietic cells and/or for the in vitro prognosis of the evolution thereof, which comprises a composition according to claim 1.

23. A combination comprising the device for the diagnosis of a neoplasia originating from hematopoietic cells and/or for the in vitro prognosis of the evolution thereof according to claim 22, and a composition in the form of microarray wherein the oligonucleotides are disposed in an ordered fashion on a solid support which is glass similar to a slide whereto the oligonucleotides are bound by covalent bonds, forming a microarray.

24. A combination comprising the device for the in vitro diagnosis of a neoplasia originating from hematopoietic cells and/or for the in vitro prognosis of the evolution thereof according to claim 22, and a composition in the form of microarray.

25. A device for the in vitro diagnosis of a neoplasia originating from hematopoietic cells and/or for the in vitro prognosis of the evolution thereof according to claim 23, wherein the neoplasia which is diagnosed or a whose evolution a prognosis is made of is chronic lymphatic leukemia.

26. A method for the in vitro diagnosis of a neoplasia originating from hematopoietic cells and/or in vitro prognosis of the evolution thereof which comprises the in vitro detection from a biological sample and the statistical analysis of the expression level of at least one significant gene for classifying the sample associated or not to said neoplasia, a gene which is selected from the group composed of GABARAP, NPM3, ABCB1, ABCB4, ABCC3, ABCC5, ABCC6, ABHD1, ABL1, ACTN1, AF1q, AKR1A1, ALDH1A1, ALK, ANK2, ANPEP, ANXA6, ANXA7, APAF1, APEX, ARHGEF2, ARS2, ASNS, ATIC, ATM, ATP50, BAX, BCL10, BCL2, BCL2A1, BCL2L1, BCL2LAA, BCL3, BCL6, BCL7A, BCL7b, BCR, BECN1, BIK, BIRC3, BIRC5, BLMH, BLR1, BLVRB, BMI1, BMP6, BRMS1, BST2, BTG1, BUB1, C21orf33, C5orfl3, CA12, CALD1, CANP2, CASC3, CASP1, CASP3, CASP4, CASP5, CASP6, CASP7, CASP8, CASP9, CAST, CATSD, CBFA2T1, CBFB, CCNA1, CCNB1, CCND1, CCND2, CCND3, CCNE1, CCR6, CCR7, CCT6A, CD14, CD19, CD2, CD22, CD24, CD28, CD33, CD34, CD36, CD38, CD3E, CD4, CD44, CD47, CD48, CD5, CD58, CD59, CD6, CD7, CD79A, CD79B, CD8, CD81, CD83, CD86, CD9, CDA, CDC25A, CDC25B, CDK2, CDK4, CDK5R1, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CDKN3, CDW52, CEBPA, CEBPB, CEBPD, CFL1, CKMT1, CKS2, CML66, COL3A1, COL4A6, CR2, CREB1, CREBBP, CRYAB, CSF2, CSF3, CSRP2, CTGF, CTSB, CUZD1, CXADR, CXCL9, CXCR3, CXCR4, CYC1, CYP1A1, CYP2A6, DAD-1, DAPK1, DCK, DDX6, DEK, DHFR, DLAD, DNAJA1, DNMT3B, DNTT, DOK1, DPF2, DPP4, DRG1, DRP2, E2F1, EB-1, EBI2, EDF1, EEF1A1, EEF1B2, EEF1D, EEF1G, EFNB1, EGFR, EGR1, EIF2B2, EIF3S2, EIF4B, EIF4E, EIF5A, ELF1, ELF4, ENPP1, EphA3, EPOR, ERBB2, ERBB4, ERCC1, ERCC2, ERCC3, ERCC5, ERCC6, ETS1, ETS2, ETV6, ETV7, EZH2, FABP5, FADD, FAIM3, FAM38A, FARP1, FAT, FCER2, FCGR3A, FCGR3B, FGFR1, FGFR3, FGR, FHIT, FKBP9, FLI1, FLJ22169, FLT3, FN1, FNTB, FOS, FUS, G1P2, GABPB2, GATA1, GATA2, GATA3, GCET2, GDI2, GGA3, GJA1, GLUD1, GNL3, GOT1, GRB2, GRIA3, GRK4, GSTP1, GSTT1, GUSB, GZMA, H2AFX, H3F.sub.3A, HCK, HELLS, HIF1A, HIST1H.sub.2BN, HLA-A, HLA-DPA1, HLA-DQA1, HLA-DRA, HLA-DRB3, HLF, HMMR, HNRPH3, HNRPL, HOXA10, HOXA9, HOXD8, HOXD9, HRAS, HSD17B1, HSPB1, IBSP, ICAM1, ICAM3, ID2, IER3, IFRD1, IGFBP2, IGFBP3, IGFIR, IGLV6-57, IL10, IL15, IL1B, IL2, IL2RA, IL3, IL32, IL3RA, IL4R, IL6, IL6R, IL8, ILF2, IRF1, IRF2, IRF4, IRF8, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAL, ITGAM, ITGAX, ITGB1, ITGB2, JAK1, JAK2, JUNB, KAI1, KIAA0247, KIAA0864, KIT, KLF1, KLF13, KRAS2, KRT18, LADH, LAG3, LASP1, LCK, LCP1, LEPR, LGALS3, LGALS7, LIF, LIMS1, LMO2, LOC285148, LRP, LSP1, LYL1, LYN, LYZ, MAFB, MAFK, MAGEA1, MAL, MAP3K12, MAP4K1, MAPK10, MAZ, MBP1, MCL1, MCM3, MCM7, MDM2, MEIS1, MEN1, MERTK, MKI67, MLF1, MLF2, MLL, MLLT10, MME, MMP2, MMP7, MMP8, MMP9, MNDA, MPL, MPO, MRPL37, MS4A1, MTCP1, MUC-1, MX1, MYB, MYBL1, MYC, MYOD1, NCALD, NCAM1, NCL, NDP52, NDRG1, NDUFA1, NDUFB, NF1, NFATC1, NFIC, NFKB1, NFKB1A, NINJ1, NPM1, NR3C1, NUMA1, NXF1, ODC1, OGGI, OLIG2, OPRD1, p14ARF, P55CDC, PABPC1, PAX5, PAX6, PAX8, PBX1, PBX3, PCA1, PCD, PCNA, PDCD1, PDGFA, PDGFRB, PDHA1, PGF, PGRMC1, PICALM, PLA2G6, PLAU, PLK1, PLP, PLS3, PLZF, PML, PMM1, POLR2c, POU2F2, PPP1CC, PRAME, PRKCl, PRKCQ, PRKDC, PRL, PRTN3, PSMA5, PSMB4, PSMC5, PSMD7, PTEN, PTGS1, PTHLH, PTK2, PTK2B, PTN, PTPRCCD, PYGB, RAD51, RAF1, RAG1, RARA, RARB, RB1, RBBP4, RBBP6, RBBP8, RBP4, RET, RGS1, RGS1, RIS1, RORA, RPL17, RPL23A, RPL24, RPL36A, RPL37A, RPL41, RPS3, RPS5, RPS9, RUNX1, RxRA, S100A2, S100A8, SDC1, SDHD, SELE, SELL, SEPW1, SERPINA9, SERPINB5, SERPNINA9, SFTPB, SIAT4A, SLC7A5, SNRPB, SOSTDC1, SP1, SPI1, SPN, SPRR1A, SREBF1, SSBP1, STAT1, STAT3, STAT5B, SUMO1, TACSTD2, TAGLN2, TAL1, TBP, TCEB1, TCF1, TCF3, TCF7, TCL1A, TCRbeta, TEGT, TERF1, TERT, TFCP2, TFRC, THBS1, THPO, TIA-2, TIAM1, TK1, TLX1, TMEM4, TNF, TNFRSF10C, TNFRSF1A, TNFRSF25, TNFRSF5, TNFRSF6, TNFRSF8, TNFSF10, TNFSF5, TNFSF6, TOP2A, TOPORS, TP73, TRA@, TRADD, TRAF3, TRAP1, TRIB2, TXNRD1, UBE2C, UHRF1, UVRAG, VCAM1, VEGF, VPREB1, WBSCR20C, WNT16, WT1, XBP1, XPO6, XRCC3, XRCC5, ZAP70, ZFPL1, ZNF42, ZNFN1A1, ZYX, 18S rRNA, 28S rRNA and whose expression level is determined by the evaluation of the concentration of its corresponding mRNA by the use of at least one probe which has a sequence complementary to a fragment of a strand of said gene, a probe which is selected from the group of oligonucleotides composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, or combinations thereof.

27. Method for the in vitro diagnosis of a neoplasia originating from hematopoietic cells and/or the in vitro prognosis of the evolution thereof according to claim 26, which additionally comprises a previous optional step of identification of genes significant for the classification of a sample as associated or not to a specific type of neoplasia originating from hematopoietic cells, a previous step which comprises the substeps of: a) deciding the possible categories wherein the sample can be classified; b) obtaining biological samples from individuals which have previously been assigned by a method different to that claimed to any of the possible classification categories, so that there are samples of each one of the possible categories; c) obtaining the total mRNA of each one of the samples; d) obtaining the corresponding total cRNA, labelled by a method which allows its subsequent detection, of at least one aliquot of each one of the samples of mRNA, an aliquot whereto is added before the obtainment of the cRNA at least one sequence of polyadenylated nucleotides of low homology with human genes for which it acts as internal positive control of the process; e) adding to one of the aliquots of cRNA which are going to be used in step f) at least one oligonucleotide of low homology with human genes different from and not complementary to any possible sequence of nucleotides which have been added in step d), for which it acts as positive hybridization control; f) hybridizing, in strict conditions, at least one aliquot of total cRNA of each one of the samples with at least one microarray which comprises at least two copies of each one of the oligonucleotides from the group composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, a microarray which additionally comprises: a. at least two points which correspond to different aliquots of the solvent wherein nucleotides are found at the time of their deposit on the surface of the microarray, for which they serve as blank, b. at least two copies of at least one oligonucleotide for each one of the polyadenylated sequences added in step d), an oligonucleotide whose sequence will correspond to a fragment, different from the polyadenylation zone, of the sequence of polyadenylated nucleotides whose evolution in the process has to be controlled; c. for each one of the oligonucleotides added in step e), at least two copies of an oligonucleotide complementary thereto; d. at least two copies of each member of at least one pair of oligonucleotides wherein the sequence of one of the members corresponds to a sequence of zone 5' and the sequence of the other corresponds to a sequence of zone 3' of the mRNA of a gene which is expressed in constitutive form in any cell of hematopoietic origin; e. at least two copies of at least one oligonucleotide of low homology with human genes different from any of the oligonucleotides defined in section b. and different from any of the synthetic oligonucleotides added optionally in step e); g) detecting and quantifying the signal of cRNA hybridized with each one of the copies of each one of the oligonucleotides present in the microarray, as well as the signal corresponding to the points of the solvent; h) calculating the average level of intensity of hybridization of each one of the oligonucleotides of the microarray calculating the average of the intensities of the copies of each one of the oligonucleotides; i) taking the hybridization as valid if the following conditions are complied with: a. the ratio between the average intensity and the average background of all the oligonucleotides of the microarray is greater than 10; b. the value of the average coefficient of variation of all the replicas of oligonucleotides should be less than 0.3; c. the average value of negative control should be less than 2.5 times the average value of the points corresponding to the solvent; d. there is a signal both in the hybridization controls and in the internal positive controls used as process control; j) normalizing the data; k) eliminating the oligonucleotides with values of average intensity minus average background noise less than approximately 2 times the average value obtained with the points corresponding to the solvent, as well as the oligonucleotides with an interquartile range of normalized intensity throughout the samples less than 0.3; l) performing the statistical analysis to find the statistically significant oligonucleotides to differentiate between the different categories and be able to classify a sample which has not been previously assigned to any category, choosing said oligonucleotides among those which have not been eliminated in the previous steps, until obtaining "n" oligonucleotides which either have a value of p less than a limit which is chosen from the open range of 0 to 0.05, preferably using for it a method with capacity to reduce false positives, or that which best defines the category established; m) checking that the grouping of the samples according to the differences in intensities between the different samples detected for the statistically significant oligonucleotides gives rise to the samples being classified in the same categories as those which had previously been assigned by a different method.

28. Method according to claim 27, wherein the microarray comprises at least four copies of each one of the oligonucleotides present in it and the average of the intensities of the copies of each one of the oligonucleotides which is calculated in h) is a trimmed mean.

29. Method according to claim 28, wherein the normalization is carried out using the "variance stabilization normalization" method available in the "vsn" package in R.

30. Method according to claim 27, wherein the statistical analysis to find the statistically significant oligonucleotides to differentiate between the different categories is carried out using the mt.maxT function of the multtest package in R.

31. Method according to claim 27, wherein the diagnosis is done with a diagnostic device which comprises a composition containing at least one oligonucleotide from the group composed of: SG1, SG2, SG3, SG4, SG5, SG6, SG7, SG8, SG9, SG10, SG11, SG12, SG13, SG14, SG15, SG16, SG17, SG18, SG19, SG20, SG21, SG22, SG23, SG24, SG25, SG26, SG27, SG28, SG29, SG30, SG31, SG32, SG33, SG34, SG35, SG36, SG37, SG38, SG39, SG40, SG41, SG42, SG43, SG44, SG45, SG46, SG47, SG48, SG49, SG50, SG51, SG52, SG53, SG54, SG55, SG56, SG57, SG58, SG59, SG60, SG61, SG62, SG63, SG64, SG65, SG66, SG67, SG68, SG69, SG70, SG71, SG72, SG73, SG74, SG75, SG76, SG77, SG78, SG79, SG80, SG81, SG82, SG83, SG84, SG85, SG86, SG87, SG88, SG89, SG90, SG91, SG92, SG93, SG94, SG95, SG96, SG97, SG98, SG99, SG100, SG101, SG102, SG103, SG104, SG105, SG106, SG107, SG108, SG109, SG110, SG111, SG112, SG113, SG114, SG115, SG116, SG117, SG118, SG119, SG120, SG121, SG122, SG123, SG124, SG125, SG126, SG127, SG128, SG129, SG130, SG131, SG132, SG133, SG134, SG135, SG136, SG137, SG138, SG139, SG140, SG141, SG142, SG143, SG144, SG145, SG146, SG147, SG148, SG149, SG150, SG151, SG152, SG153, SG154, SG155, SG156, SG157, SG158, SG159, SG160, SG161, SG162, SG163, SG164, SG165, SG166, SG167, SG168, SG169, SG170, SG171, SG172, SG173, SG174, SG175, SG176, SG177, SG178, SG179, SG180, SG181, SG182, SG183, SG184, SG185, SG186, SG187, SG188, SG189, SG190, SG191, SG192, SG193, SG194, SG195, SG196, SG197, SG198, SG199, SG200, SG201, SG202, SG203, SG204, SG205, SG206, SG207, SG208, SG209, SG210, SG211, SG212, SG213, SG214, SG215, SG216, SG217, SG218, SG219, SG220, SG221, SG222, SG223, SG224, SG225, SG226, SG227, SG228, SG229, SG230, SG231, SG232, SG233, SG234, SG235, SG236, SG237, SG238, SG239, SG240, SG241, SG242, SG243, SG244, SG245, SG246, SG247, SG248, SG249, SG250, SG251, SG252, SG253, SG254, SG255, SG256, SG257, SG258, SG259, SG260, SG261, SG262, SG263, SG264, SG265, SG266, SG267, SG268, SG269, SG270, SG271, SG272, SG273, SG274, SG275, SG276, SG277, SG278, SG279, SG280, SG281, SG282, SG283, SG284, SG285, SG286, SG287, SG288, SG289, SG290, SG291, SG292, SG293, SG294, SG295, SG296, SG297, SG298, SG299, SG300, SG301, SG302, SG303, SG304, SG305, SG306, SG307, SG308, SG309, SG310, SG311, SG312, SG313, SG314, SG315, SG316, SG317, SG318, SG319, SG320, SG321, SG322, SG323, SG324, SG325, SG326, SG327, SG328, SG329, SG330, SG331, SG332, SG333, SG334, SG335, SG336, SG337, SG338, SG339, SG340, SG341, SG342, SG343, SG344, SG345, SG346, SG347, SG348, SG349, SG350, SG351, SG352, SG353, SG354, SG355, SG356, SG357, SG358, SG359, SG360, SG361, SG362, SG363, SG364, SG365, SG366, SG367, SG368, SG369, SG370, SG371, SG372, SG373, SG374, SG375, SG376, SG377, SG378, SG379, SG380, SG381, SG382, SG383, SG384, SG385, SG386, SG387, SG388, SG389, SG390, SG391, SG392, SG393, SG394, SG395, SG396, SG397, SG398, SG399, SG400, SG401, SG402, SG403, SG404, SG405, SG406, SG407, SG408, SG409, SG410, SG411, SG412, SG413, SG414, SG415, SG416, SG417, SG418, SG419, SG420, SG421, SG422, SG423, SG424, SG425, SG426, SG427, SG428, SG429, SG430, SG431, SG432, SG433, SG434, SG435, SG436, SG437, SG438, SG439, SG440, SG441, SG442, SG443, SG444, SG445, SG446, SG447, SG448, SG449, SG450, SG451, SG452, SG453, SG454, SG455, SG456, SG457, SG458, SG459, SG460, SG461, SG462, SG465, SG468, SG469, SG470, SG471, SG472, SG473, SG474, SG475, SG476, SG477, SG478, SG479, SG480, SG481, SG482, SG483, SG484, SG485, SG486, SG487, SG488, SG489, SG490, SG491, SG492, SG493, SG494, SG495, SG496, SG497, SG498, SG499, SG500, SG501, SG502, SG503, SG504, SG505, SG506, SG507, SG508, SG509, SG510, SG511, SG512, SG513, SG514, SG515, SG516, SG517, SG518, SG519, SG520, SG521, SG522, SG523, SG524, SG525, SG526, SG527, SG428, SG529, SG530, SG531, SG532, SG533, SG534, SG535, SG536, SG537, SG538, SG539, SG540, SG541, SG542, SG543, SG544, SG545, SG546, SG547, SG548, SG549, SG550, SG551, SG552, SG553, SG554, SG555, SG556, SG557, SG558, SG559, SG560, SG561, SG562, SG563, or combinations thereof, to be used as probe in the determination of the expression level of a gene which possesses a sequence complementary to said oligonucleotide by the evaluation of the mRNA level corresponding to that gene, of application in the in vitro diagnosis of neoplasias originating from hematopoietic cells and/or in the in vitro prognosis of the evolution of said disease.

32. Method according to claim 27, which comprises an optional step of obtainment of a classification function for each sample by the arbitrary assignment of the value of 0 to one of the possible categories "a" and of the value 1 to the other possible category "b" wherein it is possible to classify the sample and the obtainment by logistical regression of a coefficient for each one of the oligonucleotides which make it possible to calculate a value x.sub.i for each sample by a function of the type: n x.sub.i=constant+.SIGMA.(coeff_olig.sub.m*Imn.sub.i.sub.--olig.sub.m) m=1 where coeff_olig.sub.m represents the coefficient calculated for a specific oligonucleotide Imn.sub.i.sub.--olig.sub.m represents the average value of normalized intensity obtained in the hybridization of the sample i calculated for the oligonucleotide "m" varies from 1 to "n" n is the total number of oligonucleotides considered significant value "x.sub.i" wherefrom the probability "p.sub.i" that a sample "i" belongs to one or another category is calculated using the formula p.sub.i=1/(1+e.sup.-xi) and classifying the sample as belonging to category "a" or "b" according to its corresponding value p.sub.i is closer to 0 or 1, respectively.

33. Method according to claim 27, wherein the statistical analysis to find the significant oligonucleotides to differentiate between the different categories is carried out using the "Nearest Shrunken Centroids" method.

34. Method according to claim 27, wherein the biological samples analysed in vitro are samples of peripheral blood.

35. Method according to claim 34, wherein a leukemia is diagnosed in vitro or a prognosis is made of the evolution thereof.

36. Method according to claim 35, wherein it is diagnosed in vitro if an individual suffers from chronic lymphatic leukemia.

37. Method according to claim 35, wherein an in vitro prognosis is made of the evolution of the chronic lymphatic leukemia in a subject classifying a sample of blood extracted therefrom as "associated to stable chronic lymphatic leukemia" or as "associated to progressive chronic lymphatic leukemia".

38. Method to make an in vitro diagnosis of a neoplasia originating from hematopoietic cells and/or an in vitro prognosis of the evolution thereof which comprises the in vitro detection and the statistical analysis of the expression level of at least one significant gene for classifying the sample as belonging to a healthy individual or associating it to a type of neoplasia originating from hematopoietic cells according to claim 26, wherein the neoplasia which is diagnosed and/or whose evolution a prognosis is made of is a leukemia.

39. Method according to claim 38, wherein a diagnosis/or prognosis is made of the evolution of the chronic lymphatic leukemia.

40. Method to make an in vitro diagnosis of chronic lymphatic leukemia and/or make an in vitro prognosis of its evolution according to claim 39, wherein the in vitro detection of the expression level of at least one significant gene is carried out from samples of peripheral blood.

41. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 40, wherein the subjects wherefrom the corresponding blood samples have been taken are classified in the category of subject not suffering from CLL or in the category of subject suffering from CLL.

42. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 41, wherein the classification of the subjects is carried out after the in vitro detection and the statistical analysis of the expression level in the corresponding blood samples of at least genes CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1.

43. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 42, wherein the classification of the subjects is carried out after the in vitro detection and the statistical analysis of the expression level in the corresponding blood samples additionally of genes IRF8 and COL3A1.

44. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 43, wherein the in vitro detection and the statistical analysis of the expression level of genes CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 is carried out by the evaluation of the corresponding mRNA by hybridization of its corresponding cRNA using as probes the oligonucleotides SG117, SG428, SG459, SG507, SG508, SG461 and SG493.

45. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 44, wherein the oligonucleotides form part of a composition in the form of microarray.

46. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 45, wherein the evaluation of the hybridized cRNA is carried out thanks to the prior labelling of cRNA with biotin, the staining of the hybridized microarray with streptavidin conjugated with a fluorophore and the detection of the signal emitted by said fluorophore.

47. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 46, wherein the fluorophore is Cy3.

48. Method to make an in vitro diagnosis of chronic lymphatic leukemia according to claim 47, wherein the classification of a subject from which the sample I has been taken analysed in the category of subject not suffering from CLL or in the category of subject suffering from CLL is carried out by calculating for said subject a value of probability p, =1/(1+e.sup.-xi) after obtaining its corresponding value of x.sub.i by the formula x.sub.i=-719.241486+(2.44756372*Imn.sub.i.sub.--CD79A)+(7.38657611*Imn.su- b.i.sub.--FAIM3)+(23.1465464*Imn.sub.i.sub.--HLA-DRA)+(43.6287742*Imn.sub.- i.sub.--IRF8)-(19.3978182*Imn.sub.i.sub.--COL3A1)-(2.80282646*Imn.sub.i.su- b.--HLA-DRB3)+(49.5345672*Imn.sub.i.sub.--HLA-DQA1) formula wherein each one of the values called abbreviation "Imn.sub.i" followed by the abbreviation of a gene makes reference to the average value of normalized intensity obtained after detecting the hybridization signal corresponding to the oligonucleotide which is being used as probe to evaluate the expression of the said gene and classifying the subject as subject not suffering from CLL if the value of p.sub.i is less than 0.5 and as subject suffering from CLL if the value of p.sub.i is greater than 0.5.

49. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to claim 40, wherein the subjects from which the corresponding blood samples have been taken are classified in the category of subject with stable CLL or in the category of subject with progressive CLL.

50. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to claim 49, wherein the classification of the subjects is carried out after the in vitro detection and the statistical analysis of the expression level in the corresponding blood samples of at least genes PSMB4, FCER2 and POU2F2.

51. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to claim 50, wherein the classification of the subjects is carried out after the in vitro detection and the statistical analysis of the expression level in the corresponding blood samples additionally of at least one gene selected from the group composed of ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4.

52. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to claim 51, wherein the classification of the subjects is carried out after the in vitro detection and the statistical analysis of the expression level in the corresponding blood samples of at least the genes of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4.

53. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to either of claims 51, wherein the in vitro detection and the statistical analysis of the expression level of the genes examined is carried out by the evaluation of the corresponding mRNA by hybridization of its corresponding cRNA using as probes the corresponding oligonucleotides selected from the group composed of SG26, SG216, SG366, SG31, SG177, SG194, SG195, SG197, SG213, SG293, SG301, SG309, SG33, SG343, SG357, SG439, SG452, SG555, SG556.

54. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to claim 53, wherein the oligonucleotides form part of a composition in the form of microarray.

55. Method to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia according to claim 54, wherein the evaluation of the corresponding mRNA of the sample analysed by the detection of the corresponding hybridized cRNA to the corresponding oligonucleotide is carried out thanks to the previous labelling of the cRNA with biotin, the staining of the microarray hybridized with streptavidin conjugated with a fluorophore and the detection of the signal emitted by said fluorophore.

56. Method to make an in vitro prognosis of the evolution of the disease in an individual suffering from chronic lymphatic leukemia according to claim 55, wherein the fluorophore is Cy3.

57. A method comprising use of a device for evaluation of the expression level of at least one gene of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4, CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 for the in vitro diagnosis of the existence of chronic lymphatic leukemia in a subject and/or for the in vitro prognosis of the evolution of the chronic lymphatic leukemia in a subject.

58. A method comprising use of a device for evaluation of the expression level of genes according to claim 57, wherein the expression level of at least one gene of the group composed of CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1, IRF8 and COL3A1 is evaluated for the in vitro diagnosis of the existence of chronic lymphatic leukemia in a subject.

59. A method comprising use of a device for evaluation of the expression level of genes according to claim 57, wherein the expression level of at least genes CD79A, FAIM3, HLA-DRA, HLA-DRB3, HLA-DQA1 is evaluated for the in vitro diagnosis of the existence of chronic lymphatic leukemia in a subject.

60. A method comprising use of a device for evaluation of the expression level of genes according to claim 59, wherein additionally the expression level of at least genes IRF8 and COL3A1 are evaluated for the in vitro diagnosis of the existence of chronic lymphatic leukemia in a subject.

61. A method comprising use of a device for evaluation of the expression level of genes according to claim 57, wherein the expression level of at least one gene of the group composed of PSMB4, FCER2, POU2F2, ODC1, CD79A, CD2, CD3E, CD5, MS4A1, EIF4E, FHIT, NR3C1, LCP1, MAPK10, ABCC5, XRCC3, CML66, PLZF, RBP4 is evaluated, to make an in vitro prognosis of the evolution of the disease in a subject suffering from chronic lymphatic leukemia.